NM_001012416.1:c.317A>T

Variant names:

• chr11-1697562-A-T
• rs759610168
• NM_001012416.1:c.317A>T

Variant summary

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

The NM_001012416.1(KRTAP5-6):​c.317A>T​(p.Gln106Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q106P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KRTAP5-6 NM_001012416.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.856
• Publications: 0 publications found

Genes affected

KRTAP5-6 (HGNC:23600): (keratin associated protein 5-6) 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=0.20108211).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012416.1. 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
	KRTAP5-6	NM_001012416.1	MANE Select	c.317A>T	p.Gln106Leu	missense	Exon 1 of 1	NP_001012416.1	Q6L8G9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-6	ENST00000382160.1	TSL:6 MANE Select	c.317A>T	p.Gln106Leu	missense	Exon 1 of 1	ENSP00000371595.1	Q6L8G9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.65
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.23	N
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		0.86
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.098
Sift4G	Uncertain	0.057	T
Polyphen		0.56	P
Vest4		0.45
MutPred		0.12		Gain of ubiquitination at K111 (P = 0.1047)
MVP		0.37
MPC		0.015
ClinPred		0.34	T
GERP RS		3.3
PromoterAI		-0.0084	Neutral
Varity_R		0.77
gMVP		0.024
Mutation Taster		=95/5	polymorphism

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: rs759610168; hg19: chr11-1718792;