rs147359482

Variant names:

• chr12-52314701-C-A
• rs147359482
• NM_002282.3:c.1412G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-52314701-C-A
• chr12-52314701-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002282.3(KRT83):​c.1412G>T​(p.Gly471Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G471D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: KRT83 NM_002282.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41
• Publications: 5 publications found

Genes affected

KRT83 (HGNC:6460): (keratin 83) The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related subfamily includes KRTHB2, KRTHB4, and KRTHB5. All hair keratins are expressed in the hair follicle; this hair keratin, as well as KRTHB1 and KRTHB6, is found primarily in the hair cortex. [provided by RefSeq, Jul 2008]

KRT83 Gene-Disease associations (from GenCC):

• monilethrix

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• erythrokeratodermia variabilis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000296556 (HGNC:58282):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT83	NM_002282.3	c.1412G>T	p.Gly471Val	missense_variant	Exon 9 of 9	ENST00000293670.3	NP_002273.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT83	ENST00000293670.3	c.1412G>T	p.Gly471Val	missense_variant	Exon 9 of 9	1	NM_002282.3	ENSP00000293670.3
ENSG00000296556	ENST00000740301.1	n.506+3069C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Uncertain	-0.040	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		3.4
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0020	B
Vest4		0.70
MutPred		0.36		Gain of catalytic residue at K474 (P = 0);
MVP		0.68
MPC		0.11
ClinPred		0.70	D
GERP RS		3.8
Varity_R		0.21
gMVP		0.21
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs147359482; hg19: chr12-52708485;