11-71527605-G-A

Variant names:

• chr11-71527605-G-A
• rs773423470
• NM_001012503.2:c.305G>A

Variant summary

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

The NM_001012503.2(KRTAP5-7):​c.305G>A​(p.Cys102Tyr) 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. 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. C102F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: KRTAP5-7 NM_001012503.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.642
• Publications: 0 publications found

Genes affected

KRTAP5-7 (HGNC:23602): (keratin associated protein 5-7) 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=0.18503183).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012503.2. 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
	KRTAP5-7	NM_001012503.2	MANE Select	c.305G>A	p.Cys102Tyr	missense	Exon 1 of 1	NP_001012521.1	Q6L8G8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-7	ENST00000398536.6	TSL:6 MANE Select	c.305G>A	p.Cys102Tyr	missense	Exon 1 of 1	ENSP00000417330.2	Q6L8G8

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 159

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.72
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.057
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		0.64
PROVEAN	Pathogenic	-8.8	D
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.90	P
Vest4		0.22
MutPred		0.40		Loss of ubiquitination at K99 (P = 0.0505)
MVP		0.28
MPC		0.011
ClinPred		0.45	T
GERP RS		1.7
PromoterAI		0.0066	Neutral
Varity_R		0.74
gMVP		0.022
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs773423470; hg19: chr11-71238651; COSMIC: COSV101273204; COSMIC: COSV101273204;