17-41097708-C-G

Variant names:

• chr17-41097708-C-G
• rs80168553
• NM_031960.3:c.377G>C

Variant summary

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

The NM_031960.3(KRTAP4-8):​c.377G>C​(p.Arg126Pro) 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. 14/22 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. R126L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 7 publications found

Genes affected

KRTAP4-8 (HGNC:17230): (keratin associated protein 4-8) Involved in aging and hair cycle. 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=0.16599658).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031960.3. 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
	KRTAP4-8	NM_031960.3	MANE Select	c.377G>C	p.Arg126Pro	missense	Exon 1 of 1	NP_114166.1	Q9BYQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-8	ENST00000333822.5	TSL:6 MANE Select	c.377G>C	p.Arg126Pro	missense	Exon 1 of 1	ENSP00000328444.4	Q9BYQ9

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000298 AC: 3 AN: 100516 AF XY: 0.0000182

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000263

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 584152 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 297768

African (AFR) AF: 0.00 AC: 0 AN: 15276

American (AMR) AF: 0.00 AC: 0 AN: 24696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13848

East Asian (EAS) AF: 0.00 AC: 0 AN: 33362

South Asian (SAS) AF: 0.00 AC: 0 AN: 47000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2196

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 386010

Other (OTH) AF: 0.00 AC: 0 AN: 28984

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000214 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.85
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.092	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-1.6
PrimateAI	Benign	0.18	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.072
Sift	Uncertain	0.019	D
Sift4G	Benign	0.065	T
Polyphen		0.93	P
Vest4		0.21
MutPred		0.49		Gain of glycosylation at S128 (P = 0.0393)
MVP		0.085
MPC		0.13
ClinPred		0.62	D
GERP RS		-2.0
PromoterAI		0.0021	Neutral
Varity_R		0.52
gMVP		0.17
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs80168553; hg19: chr17-39253960;