chr5-140537578-A-G

Position:

chr5-140537578-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017747.3(ANKHD1):c.7217A>G(p.Asn2406Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0001 in 1,583,788 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000072 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

ANKHD1
NM_017747.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.01

Variant links:

Genes affected

ANKHD1 (HGNC:24714): (ankyrin repeat and KH domain containing 1) This gene encodes a protein with multiple ankyrin repeat domains and a single KH-domain. The protein is thought to function as a scaffolding protein, and it may be involved in the regulation of caspases and thereby play an antiapoptotic role in cell survival. Alternative splicing results in multiple transcript variants, one of which generates a fusion transcript (MASK-BP3) with the downstream eIF4E-binding protein 3 (EIF4EBP3) gene, resulting in a protein comprised of the ANKHD1 sequence for the majority of the protein and a different C-terminus due to an alternate reading frame for the EIF4EBP3 segments. [provided by RefSeq, Sep 2010]

ANKHD1 links:

ANKHD1-EIF4EBP3 (HGNC:33530): (ANKHD1-EIF4EBP3 readthrough) The ANKHD1-EIF4EBP3 mRNA is an infrequent but naturally occurring readthrough transcript of the neighboring ANKHD1 and EIF4EBP3 genes. This readthrough transcript encodes a protein composed mostly of the multiple ankyrin repeats, single KH-domain protein, with its C-terminus encoded in a different reading frame from the shared portion of the EIF4EBP3 gene. The significance of this readthrough mRNA and the function of its protein product have not yet been determined. [provided by RefSeq, Nov 2009]

ANKHD1-EIF4EBP3 links:

SRA1 (HGNC:11281): (steroid receptor RNA activator 1) Both long non-coding and protein-coding RNAs are transcribed from this gene, and they represent alternatively spliced transcript variants. This gene was initially defined as a non-coding RNA, which is a coactivator for several nuclear receptors (NRs) and is associated with breast cancer. It has now been found that this gene is involved in the regulation of many NR and non-NR activities, including metabolism, adipogenesis and chromatin organization. The long non-coding RNA transcripts interact with a variety of proteins, including the protein encoded by this gene. The encoded protein acts as a transcriptional repressor by binding to the non-coding RNA. [provided by RefSeq, Mar 2012]

SRA1 links:

ANKHD1-EIF4EBP3 (HGNC:):

ANKHD1-EIF4EBP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016263962).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKHD1	NM_017747.3 linkuse as main transcript	c.7217A>G	p.Asn2406Ser	missense_variant	31/34	ENST00000360839.7	NP_060217.1	Q8IWZ3-1
ANKHD1-EIF4EBP3	NM_020690.6 linkuse as main transcript	c.7217A>G	p.Asn2406Ser	missense_variant	31/36		NP_065741.3	Q8IWZ3-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKHD1	ENST00000360839.7 linkuse as main transcript	c.7217A>G	p.Asn2406Ser	missense_variant	31/34	1	NM_017747.3	ENSP00000354085.2		Q8IWZ3-1
ANKHD1-EIF4EBP3	ENST00000532219.5 linkuse as main transcript	c.7217A>G	p.Asn2406Ser	missense_variant	31/36	2		ENSP00000432016.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000221

AC:

AN:

221682

Hom.:

AF XY:

0.000260

AC XY:

AN XY:

119274

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000564

Gnomad SAS exome

AF:

0.00168

Gnomad FIN exome

AF:

0.0000499

Gnomad NFE exome

AF:

0.0000497

Gnomad OTH exome

AF:

0.000187

GnomAD4 exome

AF:

0.000103

AC:

148

AN:

1431442

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

709688

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.0000677

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000255

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 05, 2024

The c.7217A>G (p.N2406S) alteration is located in exon 31 (coding exon 31) of the ANKHD1-EIF4EBP3 gene. This alteration results from a A to G substitution at nucleotide position 7217, causing the asparagine (N) at amino acid position 2406 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

.;T;T;T;.;.

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;D;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.016

T;T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.4

.;L;.;.;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

.;N;N;N;N;N

REVEL

Benign

0.080

Sift

Uncertain

0.026

.;D;T;T;D;D

Sift4G

Benign

0.40

T;T;T;T;T;T

Polyphen

0.45

.;P;.;.;.;.

Vest4

0.66

MutPred

0.33

.;Gain of disorder (P = 0.0356);.;.;Gain of disorder (P = 0.0356);.;

MVP

0.48

MPC

0.63

ClinPred

0.062

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over