rs200462837

Variant names:

• chr12-52235275-C-G
• NM_005556.4:c.445C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-52235275-C-G
• chr12-52235275-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005556.4(KRT7):​c.445C>G​(p.Arg149Gly) 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 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KRT7 NM_005556.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

Genes affected

KRT7 (HGNC:6445): (keratin 7) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the simple epithelia lining the cavities of the internal organs and in the gland ducts and blood vessels. The genes encoding the type II cytokeratins are clustered in a region of chromosome 12q12-q13. Alternative splicing may result in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT7	NM_005556.4	c.445C>G	p.Arg149Gly	missense_variant	Exon 2 of 9	ENST00000331817.6	NP_005547.3
KRT7	XM_011538325.3	c.445C>G	p.Arg149Gly	missense_variant	Exon 2 of 8		XP_011536627.1
KRT7	XM_047428827.1	c.445C>G	p.Arg149Gly	missense_variant	Exon 2 of 7		XP_047284783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT7	ENST00000331817.6	c.445C>G	p.Arg149Gly	missense_variant	Exon 2 of 9	1	NM_005556.4	ENSP00000329243.5
KRT7	ENST00000547613.1	n.150C>G		non_coding_transcript_exon_variant	Exon 2 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461802 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Benign	20
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.77	D
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.12	T
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.4	H
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.77		Loss of methylation at R149 (P = 0.0526);
MVP		0.63
MPC		0.89
ClinPred		1.0	D
GERP RS		-3.1
Varity_R		0.67
gMVP		0.65

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: chr12-52629059;