17-41140003-G-T

Variant names:

• chr17-41140003-G-T
• rs767233491
• NM_030976.2:c.485C>A

Variant summary

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

The NM_030976.2(KRTAP4-6):​c.485C>A​(p.Pro162Gln) 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. 13/21 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. P162L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 47)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-6 NM_030976.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

Genes affected

KRTAP4-6 (HGNC:18909): (keratin associated protein 4-6) 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=0.18692422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-6	NM_030976.2	c.485C>A	p.Pro162Gln	missense_variant	Exon 1 of 1	ENST00000345847.5	NP_112238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-6	ENST00000345847.5	c.485C>A	p.Pro162Gln	missense_variant	Exon 1 of 1	6	NM_030976.2	ENSP00000328270.5

Frequencies

GnomAD3 genomes Cov.: 47

GnomAD3 exomes AF: 0.00000811 AC: 2 AN: 246660 Hom.: 0 AF XY: 0.0000150 AC XY: 2 AN XY: 133626

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000138 AC: 2 AN: 1444792 Hom.: 0 Cov.: 304 AF XY: 0.00000139 AC XY: 1 AN XY: 718912

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 47

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.14
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0080	D
Vest4		0.31
MutPred		0.26		Loss of loop (P = 0.0603);
MVP		0.15
MPC		0.052
ClinPred		0.39	T
GERP RS		4.8
Varity_R		0.14
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs767233491; hg19: chr17-39296255;