rs777526892

Variant names:

• chr17-41477069-C-A
• NM_002280.6:c.1355G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41477069-C-A
• chr17-41477069-C-T

Variant summary

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

The NM_002280.6(KRT35):​c.1355G>T​(p.Gly452Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G452E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: KRT35 NM_002280.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

Genes affected

KRT35 (HGNC:6453): (keratin 35) 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

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=0.24412242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT35	NM_002280.6	c.1355G>T	p.Gly452Val	missense_variant	Exon 7 of 7	ENST00000246639.7	NP_002271.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT35	ENST00000246639.7	c.1355G>T	p.Gly452Val	missense_variant	Exon 7 of 7	1	NM_002280.6	ENSP00000246639.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425234 Hom.: 0 Cov.: 48 AF XY: 0.00000141 AC XY: 1 AN XY: 707386

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: 9.11e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0081	T;T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.040	N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.016	D;D
Sift4G	Benign	0.073	T;T
Polyphen		0.54	.;P
Vest4		0.40
MutPred		0.29		.;Loss of methylation at R454 (P = 0.046);
MVP		0.61
MPC		0.18
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.17
gMVP		0.66

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: chr17-39633321;