1-246842707-T-C

Position:

• chr1-246842707-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001323342.2(AHCTF1):​c.6595A>G​(p.Lys2199Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHCTF1 NM_001323342.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16

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 (HGNC:):

ACMG classification

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=0.19008696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHCTF1	NM_001323342.2	c.6595A>G	p.Lys2199Glu	missense_variant	35/36	ENST00000648844.2	NP_001310271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHCTF1	ENST00000648844.2	c.6595A>G	p.Lys2199Glu	missense_variant	35/36		NM_001323342.2	ENSP00000497061.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.6622A>G (p.K2208E) alteration is located in exon 35 (coding exon 35) of the AHCTF1 gene. This alteration results from a A to G substitution at nucleotide position 6622, causing the lysine (K) at amino acid position 2208 to be replaced by a glutamic acid (E). 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	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.089	.;.;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Benign	0.070
Sift	Uncertain	0.0050	D;D;.
Sift4G	Uncertain	0.012	D;D;.
Polyphen		0.87	P;.;P
Vest4		0.26
MutPred		0.32		.;.;Gain of ubiquitination at K2203 (P = 0.0155);
MVP		0.38
MPC		0.58
ClinPred		0.88	D
GERP RS		4.9
Varity_R		0.18
gMVP		0.13

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

Other links and lift over

dbSNP: rs1659967949; hg19: chr1-247006009;