rs2071563

Variant names:

• chr17-41462863-G-A
• rs2071563
• NM_002278.3:c.1184C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41462863-G-A
• chr17-41462863-G-C
• chr17-41462863-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002278.3(KRT32):​c.1184C>T​(p.Thr395Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,613,082 control chromosomes in the GnomAD database, including 119,823 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12180 hom., cov: 32)
  • Exomes 𝑓: 0.38 (107643 hom.)
• Consequence: KRT32 NM_002278.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 28 publications found

Genes affected

KRT32 (HGNC:6449): (keratin 32) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009404004).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT32	NM_002278.3	c.1184C>T	p.Thr395Met	missense_variant	Exon 6 of 7	ENST00000225899.4	NP_002269.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT32	ENST00000225899.4	c.1184C>T	p.Thr395Met	missense_variant	Exon 6 of 7	1	NM_002278.3	ENSP00000225899.3

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60403 AN: 151602 Hom.: 12157 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.365

GnomAD2 exomes AF: 0.381 AC: 95564 AN: 251104 AF XY: 0.376

Gnomad AFR exome AF: 0.421

Gnomad AMR exome AF: 0.391

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.339

Gnomad FIN exome AF: 0.520

Gnomad NFE exome AF: 0.381

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.382 AC: 558727 AN: 1461360 Hom.: 107643 Cov.: 72 AF XY: 0.379 AC XY: 275745 AN XY: 727006

African (AFR) AF: 0.418 AC: 13981 AN: 33468

American (AMR) AF: 0.394 AC: 17640 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 9218 AN: 26130

East Asian (EAS) AF: 0.355 AC: 14094 AN: 39698

South Asian (SAS) AF: 0.292 AC: 25193 AN: 86226

European-Finnish (FIN) AF: 0.504 AC: 26915 AN: 53406

Middle Eastern (MID) AF: 0.327 AC: 1800 AN: 5506

European-Non Finnish (NFE) AF: 0.384 AC: 427088 AN: 1111866

Other (OTH) AF: 0.378 AC: 22798 AN: 60340

GnomAD4 genome AF: 0.399 AC: 60472 AN: 151722 Hom.: 12180 Cov.: 32 AF XY: 0.403 AC XY: 29906 AN XY: 74140

African (AFR) AF: 0.418 AC: 17309 AN: 41366

American (AMR) AF: 0.413 AC: 6306 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3468

East Asian (EAS) AF: 0.344 AC: 1767 AN: 5136

South Asian (SAS) AF: 0.261 AC: 1254 AN: 4808

European-Finnish (FIN) AF: 0.519 AC: 5464 AN: 10520

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25934 AN: 67858

Other (OTH) AF: 0.365 AC: 768 AN: 2106

Alfa AF: 0.380 Hom.: 7281

Bravo AF: 0.391

TwinsUK AF: 0.387 AC: 1435

ALSPAC AF: 0.379 AC: 1462

ESP6500AA AF: 0.411 AC: 1809

ESP6500EA AF: 0.375 AC: 3226

ExAC AF: 0.375 AC: 45558

Asia WGS AF: 0.302 AC: 1052 AN: 3478

EpiCase AF: 0.374

EpiControl AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.53	D
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-1.5	T
MutationAssessor	Pathogenic	4.0	H
PhyloP100		2.4
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.12
MPC		0.56
ClinPred		0.064	T
GERP RS		5.1
Varity_R		0.32
gMVP		0.71
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2071563; hg19: chr17-39619115; COSMIC: COSV56786004;