Variant 2-196998407-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195144.2(ANKRD44):c.2678A>G(p.Asn893Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

ANKRD44
NM_001195144.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.951

Variant links:

Genes affected

ANKRD44 (HGNC:25259): (ankyrin repeat domain 44)

ANKRD44 links:

ANKRD44 (HGNC:):

ANKRD44 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09395811).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD44	NM_001195144.2 linkuse as main transcript	c.2678A>G	p.Asn893Ser	missense_variant	25/28	ENST00000282272.15	NP_001182073.1	Q8N8A2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANKRD44	ENST00000282272.15 linkuse as main transcript	c.2678A>G	p.Asn893Ser	missense_variant	25/28	5	NM_001195144.2	ENSP00000282272.9	Q8N8A2-1
ANKRD44	ENST00000424317.5 linkuse as main transcript	c.2123A>G	p.Asn708Ser	missense_variant	19/22	1		ENSP00000403415.1	H7C209
ANKRD44	ENST00000647377.1 linkuse as main transcript	c.2678A>G	p.Asn893Ser	missense_variant	25/28			ENSP00000496628.1	A0A2R8Y7Y4
ANKRD44	ENST00000328737.6 linkuse as main transcript	c.2603A>G	p.Asn868Ser	missense_variant	25/26	2		ENSP00000331516.2	Q8N8A2-4

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000998

AC:

AN:

250450

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000971

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461268

Hom.:

Cov.:

AF XY:

0.0000688

AC XY:

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000630

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000204

Hom.:

Bravo

AF:

0.000110

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

May 30, 2023

The c.2678A>G (p.N893S) alteration is located in exon 25 (coding exon 25) of the ANKRD44 gene. This alteration results from a A to G substitution at nucleotide position 2678, causing the asparagine (N) at amino acid position 893 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

0.088

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0082

.;.;T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

D;D;T;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.094

T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

-0.18

.;.;N;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.74

N;.;.;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;.;.;T

Sift4G

Benign

0.85

T;.;T;T

Vest4

0.24, 0.31

MVP

0.64

ClinPred

0.077

GERP RS

4.8

Varity_R

0.099

gMVP

0.093

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