17-41308076-T-G

Variant names:

• chr17-41308076-T-G
• rs1338795767
• NM_001146182.2:c.1178A>C

Variant summary

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

The NM_001146182.2(KRTAP16-1):​c.1178A>C​(p.Tyr393Ser) 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. Y393F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP16-1 NM_001146182.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 0 publications found

Genes affected

KRTAP16-1 (HGNC:18916): (keratin associated protein 16-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307895 (HGNC:):

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=0.09592703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP16-1	NM_001146182.2	c.1178A>C	p.Tyr393Ser	missense_variant	Exon 1 of 1	ENST00000391352.2	NP_001139654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP16-1	ENST00000391352.2	c.1178A>C	p.Tyr393Ser	missense_variant	Exon 1 of 1	6	NM_001146182.2	ENSP00000375147.1
ENSG00000307895	ENST00000829650.1	n.679-17283A>C		intron_variant	Intron 2 of 2
ENSG00000307895	ENST00000829651.1	n.333-4802A>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.4
DANN	Benign	0.81
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.028
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.038
Sift	Benign	0.24	T
Sift4G	Benign	0.098	T
Vest4		0.20
MutPred		0.35		Gain of glycosylation at Y393 (P = 0.012);
MVP		0.27
ClinPred		0.075	T
GERP RS		0.51
Varity_R		0.14
gMVP		0.19

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: rs1338795767; hg19: chr17-39464328;