NM_001012416.1:c.251G>A

Variant names:

• chr11-1697496-G-A
• rs760881715
• NM_001012416.1:c.251G>A

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.251G>A​(p.Gly84Asp) 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 1,461,802 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. G84V) 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: 0.369
• 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=0.24203098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP5-6	NM_001012416.1	c.251G>A	p.Gly84Asp	missense_variant	Exon 1 of 1	ENST00000382160.1	NP_001012416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP5-6	ENST00000382160.1	c.251G>A	p.Gly84Asp	missense_variant	Exon 1 of 1	6	NM_001012416.1	ENSP00000371595.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461802 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.40
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		0.37
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.054
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.29
MutPred		0.13		Loss of phosphorylation at S82 (P = 0.2536);
MVP		0.32
MPC		0.016
ClinPred		0.47	T
GERP RS		2.8
PromoterAI		0.0084	Neutral
Varity_R		0.36
gMVP		0.011
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs760881715; hg19: chr11-1718726;