rs202015820

Variant names:

• chr11-62491750-C-A
• rs202015820
• ENST00000257247.11:c.424G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-62491750-C-A
• chr11-62491750-C-T

Variant summary

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

The NM_024060.4(AHNAK):​c.424G>T​(p.Val142Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V142I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AHNAK NM_024060.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

Genes affected

AHNAK (HGNC:347): (AHNAK nucleoprotein) The protein encoded by this gene is a large (700 kDa) structural scaffold protein consisting of a central domain with 128 aa repeats. The encoded protein may play a role in such diverse processes as blood-brain barrier formation, cell structure and migration, cardiac calcium channel regulation, and tumor metastasis. A much shorter variant encoding a 17 kDa isoform exists for this gene, and the shorter isoform initiates a feedback loop that regulates alternative splicing of this gene. [provided by RefSeq, Oct 2016]

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=0.07373452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHNAK	NM_024060.4	c.424G>T	p.Val142Phe	missense_variant	Exon 5 of 6		NP_076965.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHNAK	ENST00000257247.11	c.424G>T	p.Val142Phe	missense_variant	Exon 5 of 6	1		ENSP00000257247.7
AHNAK	ENST00000530124.5	c.342+43253G>T		intron_variant	Intron 2 of 2	3		ENSP00000433789.1
AHNAK	ENST00000525875.1	n.430G>T		non_coding_transcript_exon_variant	Exon 2 of 3	3
AHNAK	ENST00000533365.5	c.*61G>T		downstream_gene_variant		5		ENSP00000433635.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459730 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725886

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.95
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.10
Sift	Benign	0.070	T
Sift4G	Benign	0.15	T
Vest4		0.35
MutPred		0.098		Loss of glycosylation at T144 (P = 0.0853);
MVP		0.088
ClinPred		0.10	T
GERP RS		0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs202015820; hg19: chr11-62259222;