chr17-41097553-C-G

Variant names:

• chr17-41097553-C-G
• rs146385966
• NM_031960.3:c.532G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_031960.3(KRTAP4-8):​c.532G>C​(p.Val178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000871 in 1,561,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V178M) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.36
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03542283).
• BP6: Variant 17-41097553-C-G is Benign according to our data. Variant chr17-41097553-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2517996.Status of the report is criteria_provided_single_submitter, 1 stars.

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.532G>C	p.Val178Leu	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.532G>C	p.Val178Leu	missense	Exon 1 of 1	ENSP00000328444.4	Q9BYQ9

Frequencies

GnomAD3 genomes AF: 0.0000805 AC: 12 AN: 149046 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000281 AC: 5 AN: 177990 AF XY: 0.0000424

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000541

Gnomad OTH exome AF: 0.000205

GnomAD4 exome AF: 0.0000878 AC: 124 AN: 1412684 Hom.: 0 Cov.: 88 AF XY: 0.0000916 AC XY: 64 AN XY: 698616

African (AFR) AF: 0.0000353 AC: 1 AN: 28368

American (AMR) AF: 0.00 AC: 0 AN: 37442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25258

East Asian (EAS) AF: 0.00 AC: 0 AN: 37320

South Asian (SAS) AF: 0.00 AC: 0 AN: 81174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.000106 AC: 115 AN: 1088404

Other (OTH) AF: 0.000137 AC: 8 AN: 58476

GnomAD4 genome AF: 0.0000805 AC: 12 AN: 149046 Hom.: 0 Cov.: 32 AF XY: 0.0000824 AC XY: 6 AN XY: 72786

African (AFR) AF: 0.0000260 AC: 1 AN: 38516

American (AMR) AF: 0.00 AC: 0 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.0000443 Hom.: 7

Bravo AF: 0.0000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.061
DANN	Benign	0.71
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.0095	T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.025	N
PhyloP100		-3.4
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.0070
Sift	Benign	0.41	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.035
MVP		0.014
MPC		0.088
ClinPred		0.017	T
GERP RS		-4.1
Varity_R		0.032
gMVP		0.059
Mutation Taster		=100/0	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: rs146385966; hg19: chr17-39253805;