17-41168066-C-G

Variant names:

• chr17-41168066-C-G
• NM_033187.2:c.107G>C

Variant summary

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

The NM_033187.2(KRTAP4-3):​c.107G>C​(p.Arg36Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRTAP4-3 NM_033187.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.135

Genes affected

KRTAP4-3 (HGNC:18908): (keratin associated protein 4-3) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.14309227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-3	NM_033187.2	c.107G>C	p.Arg36Thr	missense_variant	Exon 1 of 1	ENST00000391356.4	NP_149443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-3	ENST00000391356.4	c.107G>C	p.Arg36Thr	missense_variant	Exon 1 of 1	6	NM_033187.2	ENSP00000375151.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.107G>C (p.R36T) alteration is located in exon 1 (coding exon 1) of the KRTAP4-3 gene. This alteration results from a G to C substitution at nucleotide position 107, causing the arginine (R) at amino acid position 36 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.13
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Benign	0.19	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.073
Sift	Benign	0.13	T
Sift4G	Uncertain	0.058	T
Polyphen		0.84	P
Vest4		0.33
MutPred		0.51		Loss of phosphorylation at T33 (P = 0.111);
MVP		0.055
MPC		0.028
ClinPred		0.66	D
GERP RS		0.80
Varity_R		0.27
gMVP		0.068

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-39324318;