rs151023228

Variant names:

• chr17-41395280-C-A
• rs151023228
• NM_002277.3:c.841G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41395280-C-A
• chr17-41395280-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002277.3(KRT31):​c.841G>T​(p.Ala281Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,612,992 control chromosomes in the GnomAD database, including 4 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A281T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (2 hom.)
• Consequence: KRT31 NM_002277.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.312
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019213587).
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.841G>T	p.Ala281Ser	missense	Exon 5 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.841G>T	p.Ala281Ser	missense	Exon 5 of 7	ENSP00000251645.2	Q15323

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 173 AN: 152204 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00113 AC: 285 AN: 251444 AF XY: 0.00114

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00182

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00118 AC: 1725 AN: 1460670 Hom.: 2 Cov.: 32 AF XY: 0.00113 AC XY: 822 AN XY: 726670

African (AFR) AF: 0.000239 AC: 8 AN: 33440

American (AMR) AF: 0.00159 AC: 71 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: 0.000383 AC: 33 AN: 86194

European-Finnish (FIN) AF: 0.000168 AC: 9 AN: 53420

Middle Eastern (MID) AF: 0.00273 AC: 13 AN: 4764

European-Non Finnish (NFE) AF: 0.00136 AC: 1508 AN: 1112010

Other (OTH) AF: 0.00136 AC: 82 AN: 60282

GnomAD4 genome AF: 0.00114 AC: 173 AN: 152322 Hom.: 2 Cov.: 32 AF XY: 0.00119 AC XY: 89 AN XY: 74484

African (AFR) AF: 0.000433 AC: 18 AN: 41568

American (AMR) AF: 0.00261 AC: 40 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00150 AC: 102 AN: 68036

Other (OTH) AF: 0.00285 AC: 6 AN: 2106

Alfa AF: 0.000833 Hom.: 0

Bravo AF: 0.00147

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00123 AC: 150

EpiCase AF: 0.00153

EpiControl AF: 0.00166

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	0.090
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.51	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.31
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.27
Sift	Benign	0.069	T
Sift4G	Benign	0.31	T
Polyphen		0.39	B
Vest4		0.21
MVP		0.30
MPC		0.59
ClinPred		0.024	T
GERP RS		5.5
Varity_R		0.22
gMVP		0.21
Mutation Taster		=99/1	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

dbSNP: rs151023228; hg19: chr17-39551532; COSMIC: COSV99078663;