chr11-62517383-C-T

Variant names:

• chr11-62517383-C-T
• NM_001620.3:c.17034G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001620.3(AHNAK):​c.17034G>A​(p.Met5678Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHNAK NM_001620.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.94
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.01648748).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001620.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHNAK	NM_001620.3	MANE Select	c.17034G>A	p.Met5678Ile	missense	Exon 5 of 5	NP_001611.1	Q09666-1
	AHNAK	NM_001346445.2		c.17034G>A	p.Met5678Ile	missense	Exon 5 of 5	NP_001333374.1	Q09666-1
	AHNAK	NM_001346446.2		c.17034G>A	p.Met5678Ile	missense	Exon 5 of 5	NP_001333375.1	Q09666-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHNAK	ENST00000378024.9	TSL:2 MANE Select	c.17034G>A	p.Met5678Ile	missense	Exon 5 of 5	ENSP00000367263.4	Q09666-1
	AHNAK	ENST00000257247.11	TSL:1	c.342+17620G>A		intron	N/A	ENSP00000257247.7	Q09666-2
	AHNAK	ENST00000530124.5	TSL:3	c.342+17620G>A		intron	N/A	ENSP00000433789.1	E9PJC6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.30
DANN	Benign	0.94
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.20	N
PhyloP100		-3.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.028
Sift	Benign	0.38	T
Sift4G	Uncertain	0.016	D
Polyphen		0.0020	B
Vest4		0.11
MutPred		0.44		Loss of catalytic residue at V5674 (P = 0.0205)
MVP		0.040
MPC		0.028
ClinPred		0.23	T
GERP RS		-4.6
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Varity_R		0.034
gMVP		0.042
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr11-62284855; COSMIC: COSV105078981; COSMIC: COSV105078981;