chr17-41308076-T-C

Variant names:

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

Variant summary

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

The NM_001146182.2(KRTAP16-1):​c.1178A>G​(p.Tyr393Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,398,348 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KRTAP16-1 NM_001146182.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 1 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: 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=0.06490335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP16-1	NM_001146182.2	c.1178A>G	p.Tyr393Cys	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>G	p.Tyr393Cys	missense_variant	Exon 1 of 1	6	NM_001146182.2	ENSP00000375147.1
ENSG00000307895	ENST00000829650.1	n.679-17283A>G		intron_variant	Intron 2 of 2
ENSG00000307895	ENST00000829651.1	n.333-4802A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1398348 Hom.: 0 Cov.: 39 AF XY: 0.00000145 AC XY: 1 AN XY: 689702

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078984

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.4
DANN	Benign	0.95
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.091	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.60	N
PhyloP100		-0.028
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.046
Sift	Benign	0.26	T
Sift4G	Benign	0.072	T
Vest4		0.14
MutPred		0.36		Loss of phosphorylation at Y393 (P = 0.0705);
MVP		0.085
ClinPred		0.051	T
GERP RS		0.51
Varity_R		0.069
gMVP		0.15
Mutation Taster		=96/4	polymorphism

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: rs1338795767; hg19: chr17-39464328;