17-41167884-T-G

Variant names:

• chr17-41167884-T-G
• rs779930379
• NM_033187.2:c.289A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033187.2(KRTAP4-3):​c.289A>C​(p.Thr97Pro) 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. 16/22 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. T97A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 29)
• Consequence: KRTAP4-3 NM_033187.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.72
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030680478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-3	NM_033187.2	c.289A>C	p.Thr97Pro	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.289A>C	p.Thr97Pro	missense_variant	Exon 1 of 1	6	NM_033187.2	ENSP00000375151.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0050
DANN	Benign	0.048
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.057	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.77	N
PhyloP100		-8.7
PrimateAI	Benign	0.21	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.020
Sift	Benign	1.0	T
Sift4G	Benign	0.71	T
Polyphen		0.0	B
Vest4		0.052
MutPred		0.41		Gain of loop (P = 0.1069);
MVP		0.030
MPC		0.026
ClinPred		0.068	T
GERP RS		-9.2
PromoterAI		0.033	Neutral
Varity_R		0.058
gMVP		0.033

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: rs779930379; hg19: chr17-39324136;