rs137989633

Variant names:

• chr12-52544644-A-G
• NM_033448.3:c.1460T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-52544644-A-G
• chr12-52544644-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033448.3(KRT71):​c.1460T>C​(p.Val487Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. V487E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRT71 NM_033448.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

Genes affected

KRT71 (HGNC:28927): (keratin 71) Keratins are intermediate filament proteins responsible for the structural integrity of epithelial cells and are subdivided into epithelial keratins and hair keratins. This gene encodes a protein that is expressed in the inner root sheath of hair follicles. The type II keratins are clustered in a region of chromosome 12q13.[provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07435155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT71	NM_033448.3	c.1460T>C	p.Val487Ala	missense_variant	Exon 9 of 9	ENST00000267119.6	NP_258259.1
KRT71	XM_047428197.1	c.1334T>C	p.Val445Ala	missense_variant	Exon 8 of 8		XP_047284153.1
KRT71	XM_017018749.2	c.1214T>C	p.Val405Ala	missense_variant	Exon 10 of 10		XP_016874238.1
KRT71	XM_047428196.1	c.1030-295T>C		intron_variant	Intron 6 of 6		XP_047284152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT71	ENST00000267119.6	c.1460T>C	p.Val487Ala	missense_variant	Exon 9 of 9	1	NM_033448.3	ENSP00000267119.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461784 Hom.: 0 Cov.: 57 AF XY: 0.00000275 AC XY: 2 AN XY: 727188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Benign	0.77
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.24
Sift	Benign	1.0	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.38
MutPred		0.36		Gain of catalytic residue at V490 (P = 0.0024);
MVP		0.60
MPC		0.11
ClinPred		0.15	T
GERP RS		2.9
Varity_R		0.074
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-52938428;