11-71538297-G-C

Variant names:

• chr11-71538297-G-C
• rs777866571
• NM_021046.3:c.242G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021046.3(KRTAP5-8):​c.242G>C​(p.Gly81Ala) 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. 14/21 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. G81D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP5-8 NM_021046.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987
• Publications: 0 publications found

Genes affected

KRTAP5-8 (HGNC:23603): (keratin associated protein 5-8) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000307649 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06365901).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021046.3. 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
	KRTAP5-8	NM_021046.3	MANE Select	c.242G>C	p.Gly81Ala	missense	Exon 1 of 1	NP_066384.2	O75690

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-8	ENST00000398534.4	TSL:6 MANE Select	c.242G>C	p.Gly81Ala	missense	Exon 1 of 1	ENSP00000420723.1	O75690
	ENSG00000307649	ENST00000827665.1		n.-181C>G		upstream_gene	N/A
	ENSG00000307649	ENST00000827666.1		n.-221C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 145

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.16
DANN	Benign	0.71
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.99
PROVEAN	Benign	0.10	N
REVEL	Benign	0.066
Sift	Benign	0.21	T
Sift4G	Benign	0.24	T
Polyphen		0.23	B
Vest4		0.16
MutPred		0.24		Gain of glycosylation at S76 (P = 0.1185)
MVP		0.085
MPC		0.047
ClinPred		0.13	T
GERP RS		1.6
PromoterAI		0.0058	Neutral
Varity_R		0.044
gMVP		0.027
Mutation Taster		=97/3	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: rs777866571; hg19: chr11-71249343;