rs201697455

Variant names:

• chr17-41394020-C-T
• rs201697455
• NM_002277.3:c.1247G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-41394020-C-T
• chr17-41394020-C-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.1247G>A​(p.Arg416His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000663 in 1,612,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. R416C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000069 (0 hom.)
• Consequence: KRT31 NM_002277.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.283
• 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=0.12846875).

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.1247G>A	p.Arg416His	missense	Exon 7 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.1247G>A	p.Arg416His	missense	Exon 7 of 7	ENSP00000251645.2	Q15323

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000401 AC: 10 AN: 249646 AF XY: 0.0000370

Gnomad AFR exome AF: 0.0000620

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000797

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000691 AC: 101 AN: 1460678 Hom.: 0 Cov.: 32 AF XY: 0.0000743 AC XY: 54 AN XY: 726582

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.0000882 AC: 98 AN: 1111712

Other (OTH) AF: 0.0000497 AC: 3 AN: 60366

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74306

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000469 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.0079
Eigen_PC	Benign	0.035
FATHMM_MKL	Benign	0.084	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.28
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.25
Sift	Benign	0.15	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.19
MVP		0.43
MPC		0.74
ClinPred		0.19	T
GERP RS		5.4
Varity_R		0.041
gMVP		0.13
Mutation Taster		=94/6	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: rs201697455; hg19: chr17-39550272;