17-41308079-G-C

Variant names:

• chr17-41308079-G-C
• rs1277407049
• NM_001146182.2:c.1175C>G

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.1175C>G​(p.Ser392Cys) 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. 15/22 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. S392F) 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: 2.07
• 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=0.092232585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146182.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP16-1	NM_001146182.2	MANE Select	c.1175C>G	p.Ser392Cys	missense	Exon 1 of 1	NP_001139654.1	A8MUX0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP16-1	ENST00000391352.2	TSL:6 MANE Select	c.1175C>G	p.Ser392Cys	missense	Exon 1 of 1	ENSP00000375147.1	A8MUX0
	ENSG00000307895	ENST00000829650.1		n.679-17286C>G		intron	N/A
	ENSG00000307895	ENST00000829651.1		n.333-4805C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.43	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.089
Sift	Benign	0.21	T
Sift4G	Benign	0.30	T
Vest4		0.15
MutPred		0.41		Loss of phosphorylation at S392 (P = 0.0192)
MVP		0.040
ClinPred		0.18	T
GERP RS		4.1
Varity_R		0.071
gMVP		0.14

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: rs1277407049; hg19: chr17-39464331;