chr17-41140373-T-G

Variant names:

• chr17-41140373-T-G
• NM_030976.2:c.115A>C

Variant summary

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

The NM_030976.2(KRTAP4-6):​c.115A>C​(p.Ser39Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP4-6 NM_030976.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.610
• Publications: 0 publications found

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

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=0.24385187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-6	NM_030976.2	c.115A>C	p.Ser39Arg	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.115A>C	p.Ser39Arg	missense_variant	Exon 1 of 1	6	NM_030976.2	ENSP00000328270.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.115A>C (p.S39R) alteration is located in exon 1 (coding exon 1) of the KRTAP4-6 gene. This alteration results from a A to C substitution at nucleotide position 115, causing the serine (S) at amino acid position 39 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T
Eigen	Benign	0.089
Eigen_PC	Benign	-0.0053
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		-0.61
PrimateAI	Benign	0.20	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.056
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.011	D
Vest4		0.19
MutPred		0.37		Gain of sheet (P = 0.0344);
MVP		0.25
MPC		0.060
ClinPred		0.96	D
GERP RS		3.4
PromoterAI		0.0086	Neutral
Varity_R		0.29
gMVP		0.20

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

hg19: chr17-39296625;