Variant chr1-246849956-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001323342.2(AHCTF1):c.6050G>T(p.Ser2017Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

AHCTF1
NM_001323342.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0110

Variant links:

Genes affected

AHCTF1 (HGNC:24618): (AT-hook containing transcription factor 1) Predicted to enable DNA binding activity. Involved in nuclear pore complex assembly and regulation of cytokinesis. Located in nuclear membrane. Colocalizes with chromatin; kinetochore; and nuclear pore outer ring. [provided by Alliance of Genome Resources, Apr 2022]

AHCTF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015679806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCTF1	NM_001323342.2 linkuse as main transcript	c.6050G>T	p.Ser2017Ile	missense_variant	33/36	ENST00000648844.2	NP_001310271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCTF1	ENST00000648844.2 linkuse as main transcript	c.6050G>T	p.Ser2017Ile	missense_variant	33/36		NM_001323342.2	ENSP00000497061	A2	Q8WYP5-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000877

AC:

AN:

250720

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461636

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000857

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.000107

AC:

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 17, 2023

The c.6077G>T (p.S2026I) alteration is located in exon 33 (coding exon 33) of the AHCTF1 gene. This alteration results from a G to T substitution at nucleotide position 6077, causing the serine (S) at amino acid position 2026 to be replaced by an isoleucine (I). 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

0.093

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.0

DANN

Benign

0.66

DEOGEN2

Benign

0.061

.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

.;.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.3

N;N;.

REVEL

Benign

0.060

Sift

Uncertain

0.028

D;D;.

Sift4G

Benign

0.17

T;T;.

Polyphen

0.60

P;.;P

Vest4

0.18

MutPred

0.31

.;.;Loss of phosphorylation at S2017 (P = 0.0341);

MVP

0.13

MPC

0.31

ClinPred

0.051

GERP RS

-4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.047

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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