NM_033187.2:c.424C>A

Variant names:

• chr17-41167749-G-T
• rs187748672
• NM_033187.2:c.424C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033187.2(KRTAP4-3):​c.424C>A​(p.Pro142Thr) 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. 14/22 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. P142L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP4-3 NM_033187.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079832256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-3	NM_033187.2	c.424C>A	p.Pro142Thr	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.424C>A	p.Pro142Thr	missense_variant	Exon 1 of 1	6	NM_033187.2	ENSP00000375151.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.1
DANN	Benign	0.68
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.079	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		0.045
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.062
Sift	Benign	0.046	D
Sift4G	Uncertain	0.044	D
Polyphen		0.12	B
Vest4		0.11
MVP		0.10
MPC		0.025
ClinPred		0.16	T
GERP RS		-0.15
PromoterAI		-0.024	Neutral
Varity_R		0.098
gMVP		0.065

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

Other links and lift over

dbSNP: rs187748672; hg19: chr17-39324001;