17-41487394-G-A

Variant names:

• chr17-41487394-G-A
• rs2301354
• NM_003771.5:c.944C>T
• KRT36 p.Thr315Met

Variant summary

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

The NM_003771.5(KRT36):​c.944C>T​(p.Thr315Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,612,810 control chromosomes in the GnomAD database, including 240,108 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 0.50 (19674 hom., cov: 33)
  • Exomes 𝑓: 0.55 (220434 hom.)
• Consequence: KRT36 NM_003771.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646
• Publications: 32 publications found

Genes affected

KRT36 (HGNC:6454): (keratin 36) The protein encoded by this gene is a member of the keratin gene family. This type I hair keratin 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=9.09239E-5).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003771.5. 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
	KRT36	NM_003771.5	MANE Select	c.944C>T	p.Thr315Met	missense	Exon 5 of 7	NP_003762.1	O76013-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT36	ENST00000328119.11	TSL:2 MANE Select	c.944C>T	p.Thr315Met	missense	Exon 5 of 7	ENSP00000329165.6	O76013-1
	KRT36	ENST00000393986.2	TSL:1	c.794C>T	p.Thr265Met	missense	Exon 6 of 8	ENSP00000377555.2	O76013-2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76389 AN: 151988 Hom.: 19663 Cov.: 33

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.519

GnomAD2 exomes AF: 0.546 AC: 136215 AN: 249640 AF XY: 0.553

Gnomad AFR exome AF: 0.406

Gnomad AMR exome AF: 0.593

Gnomad ASJ exome AF: 0.554

Gnomad EAS exome AF: 0.349

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.556

GnomAD4 exome AF: 0.546 AC: 798076 AN: 1460706 Hom.: 220434 Cov.: 60 AF XY: 0.551 AC XY: 400237 AN XY: 726618

African (AFR) AF: 0.394 AC: 13185 AN: 33456

American (AMR) AF: 0.581 AC: 25930 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 14445 AN: 26132

East Asian (EAS) AF: 0.318 AC: 12611 AN: 39682

South Asian (SAS) AF: 0.662 AC: 57037 AN: 86200

European-Finnish (FIN) AF: 0.533 AC: 28366 AN: 53228

Middle Eastern (MID) AF: 0.574 AC: 3171 AN: 5524

European-Non Finnish (NFE) AF: 0.550 AC: 610804 AN: 1111556

Other (OTH) AF: 0.539 AC: 32527 AN: 60328

GnomAD4 genome AF: 0.502 AC: 76428 AN: 152104 Hom.: 19674 Cov.: 33 AF XY: 0.501 AC XY: 37228 AN XY: 74372

African (AFR) AF: 0.407 AC: 16868 AN: 41470

American (AMR) AF: 0.510 AC: 7806 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1908 AN: 3472

East Asian (EAS) AF: 0.338 AC: 1746 AN: 5166

South Asian (SAS) AF: 0.649 AC: 3133 AN: 4828

European-Finnish (FIN) AF: 0.524 AC: 5543 AN: 10582

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37614 AN: 67980

Other (OTH) AF: 0.515 AC: 1084 AN: 2106

Alfa AF: 0.538 Hom.: 54834

Bravo AF: 0.498

Asia WGS AF: 0.479 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.077
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.000091	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.65
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Varity_R		0.40
gMVP		0.39
Mutation Taster		=95/5	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2301354;

hg19: chr17-39643646;

COSMIC: COSV60202614;