Variant chr1-246840823-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001323342.2(AHCTF1):c.6784C>T(p.Arg2262Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000789 in 1,597,172 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

AHCTF1
NM_001323342.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.68

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCTF1	NM_001323342.2 linkuse as main transcript	c.6784C>T	p.Arg2262Cys	missense_variant	36/36	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.6784C>T	p.Arg2262Cys	missense_variant	36/36		NM_001323342.2	ENSP00000497061	A2	Q8WYP5-1
AHCTF1	ENST00000326225.3 linkuse as main transcript	c.6811C>T	p.Arg2271Cys	missense_variant	36/36	1		ENSP00000355465	P2	Q8WYP5-3
AHCTF1	ENST00000470300.5 linkuse as main transcript	n.5316C>T		non_coding_transcript_exon_variant	26/26	1
AHCTF1	ENST00000366508.5 linkuse as main transcript	c.6889C>T	p.Arg2297Cys	missense_variant	36/36	5		ENSP00000355464	A2	Q8WYP5-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152080

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:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000803

AC:

AN:

236716

Hom.:

AF XY:

0.000101

AC XY:

AN XY:

128198

show subpopulations

Gnomad AFR exome

AF:

0.0000636

Gnomad AMR exome

AF:

0.0000664

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000640

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000837

AC:

121

AN:

1445092

Hom.:

Cov.:

AF XY:

0.0000905

AC XY:

AN XY:

718050

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.0000245

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000795

Gnomad4 OTH exome

AF:

0.0000837

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000824

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.6811C>T (p.R2271C) alteration is located in exon 36 (coding exon 36) of the AHCTF1 gene. This alteration results from a C to T substitution at nucleotide position 6811, causing the arginine (R) at amino acid position 2271 to be replaced by a cysteine (C). 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

Pathogenic

0.76

BayesDel_addAF

Benign

-0.0088

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.36

.;.;T

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.6

.;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.8

D;D;.

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

D;.;D

Vest4

0.64

MutPred

0.36

.;.;Loss of methylation at K2264 (P = 0.0787);

MVP

0.53

MPC

1.0

ClinPred

0.70

GERP RS

4.8

Varity_R

0.41

gMVP

0.43

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