17-41395005-C-T

Variant names:

• chr17-41395005-C-T
• rs753334304
• NM_002277.3:c.940G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002277.3(KRT31):​c.940G>A​(p.Val314Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. V314L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KRT31 NM_002277.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696
• Publications: 0 publications found

Genes affected

KRT31 (HGNC:6448): (keratin 31) The protein encoded by this gene is a member of the keratin gene family. As a type I hair keratin, it is an acidic protein which heterodimerizes with type II keratins to form hair and nails. The type I hair keratins are clustered in a region of chromosome 17q12-q21 and have the same direction of transcription. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0836218).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002277.3. 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
	KRT31	NM_002277.3	MANE Select	c.940G>A	p.Val314Met	missense	Exon 6 of 7	NP_002268.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT31	ENST00000251645.3	TSL:1 MANE Select	c.940G>A	p.Val314Met	missense	Exon 6 of 7	ENSP00000251645.2	Q15323

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.044
DANN	Benign	0.83
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-0.70
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	0.54	T
Polyphen		0.030	B
Vest4		0.24
MutPred		0.50		Gain of phosphorylation at S312 (P = 0.211)
MVP		0.29
MPC		0.27
ClinPred		0.32	T
GERP RS		2.5
Varity_R		0.030
gMVP		0.33

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

dbSNP: rs753334304; hg19: chr17-39551257;