6-34981799-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_015245.3(ANKS1A):c.545T>G(p.Phe182Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKS1A NM_015245.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

Genes affected

ANKS1A (HGNC:20961): (ankyrin repeat and sterile alpha motif domain containing 1A) Predicted to enable ephrin receptor binding activity. Predicted to be involved in ephrin receptor signaling pathway; neuron remodeling; and substrate-dependent cell migration. Predicted to act upstream of or within negative regulation of ubiquitin-dependent protein catabolic process and regulation of ephrin receptor signaling pathway. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ANKS1A

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS1A	NM_015245.3	c.545T>G	p.Phe182Cys	missense_variant	4/24	ENST00000360359.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS1A	ENST00000360359.5	c.545T>G	p.Phe182Cys	missense_variant	4/24	1	NM_015245.3
ANKS1A	ENST00000649117.1	c.608T>G	p.Phe203Cys	missense_variant	5/25			P1
ANKS1A	ENST00000650178.1	c.608T>G	p.Phe203Cys	missense_variant	5/10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 32

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

Apr 18, 2023

The c.545T>G (p.F182C) alteration is located in exon 4 (coding exon 4) of the ANKS1A gene. This alteration results from a T to G substitution at nucleotide position 545, causing the phenylalanine (F) at amino acid position 182 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	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;T;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.66	D;D;D
MetaSVM	Benign	-0.54	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
Polyphen		1.0	.;D;.
Vest4		0.76
MutPred		0.66		.;Gain of methylation at K181 (P = 0.0415);.;
MVP		0.84
MPC		2.5
ClinPred		0.85	D
GERP RS		6.0
Varity_R		0.074
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-34949576;