Variant chr1-246850241-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001323342.2(AHCTF1):c.5765A>G(p.Asp1922Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 1,613,970 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 24 hom. )

Consequence

AHCTF1
NM_001323342.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.10

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028435588).

BP6

Variant 1-246850241-T-C is Benign according to our data. Variant chr1-246850241-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640237.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 24 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCTF1	NM_001323342.2 linkuse as main transcript	c.5765A>G	p.Asp1922Gly	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.5765A>G	p.Asp1922Gly	missense_variant	33/36		NM_001323342.2	ENSP00000497061	A2	Q8WYP5-1

Frequencies

GnomAD3 genomes

AF:

0.00305

AC:

465

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00488

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00352

AC:

882

AN:

250882

Hom.:

AF XY:

0.00377

AC XY:

511

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.000986

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00392

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00505

Gnomad OTH exome

AF:

0.00671

GnomAD4 exome

AF:

0.00441

AC:

6446

AN:

1461636

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

3294

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00586

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00431

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00484

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.00305

AC:

465

AN:

152334

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00488

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00484

Hom.:

Bravo

AF:

0.00302

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00332

AC:

403

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00567

EpiControl

AF:

0.00528

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

AHCTF1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.15

.;.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.47

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.010

Sift

Benign

0.10

T;T;.

Sift4G

Benign

0.12

T;T;.

Polyphen

0.0020

B;.;B

Vest4

0.15

MVP

0.18

MPC

0.33

ClinPred

0.0045

GERP RS

2.1

Varity_R

0.075

gMVP

0.17

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