chr17-41097858-T-C

Variant names:

• chr17-41097858-T-C
• rs1407887023
• NM_031960.3:c.227A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_031960.3(KRTAP4-8):​c.227A>G​(p.Lys76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00096 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000095 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-8 NM_031960.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.66
• Publications: 2 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0141225755).
• BP6: Variant 17-41097858-T-C is Benign according to our data. Variant chr17-41097858-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2286835.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.227A>G	p.Lys76Arg	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.227A>G	p.Lys76Arg	missense	Exon 1 of 1	ENSP00000328444.4	Q9BYQ9

Frequencies

GnomAD3 genomes AF: 0.000934 AC: 36 AN: 38524 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000497

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.000932

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00228

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000777

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 205520 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000954 AC: 115 AN: 1205730 Hom.: 0 Cov.: 162 AF XY: 0.000114 AC XY: 68 AN XY: 594650

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24594

American (AMR) AF: 0.000413 AC: 13 AN: 31446

Ashkenazi Jewish (ASJ) AF: 0.000109 AC: 2 AN: 18266

East Asian (EAS) AF: 0.0000364 AC: 1 AN: 27462

South Asian (SAS) AF: 0.000458 AC: 28 AN: 61078

European-Finnish (FIN) AF: 0.000149 AC: 5 AN: 33590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4048

European-Non Finnish (NFE) AF: 0.0000605 AC: 58 AN: 959458

Other (OTH) AF: 0.000175 AC: 8 AN: 45788

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000959 AC: 37 AN: 38584 Hom.: 0 Cov.: 0 AF XY: 0.000985 AC XY: 19 AN XY: 19284

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00146 AC: 13 AN: 8892

American (AMR) AF: 0.000494 AC: 2 AN: 4050

Ashkenazi Jewish (ASJ) AF: 0.00118 AC: 1 AN: 848

East Asian (EAS) AF: 0.000934 AC: 2 AN: 2142

South Asian (SAS) AF: 0.00 AC: 0 AN: 1716

European-Finnish (FIN) AF: 0.00228 AC: 5 AN: 2194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 56

European-Non Finnish (NFE) AF: 0.000777 AC: 14 AN: 18008

Other (OTH) AF: 0.00 AC: 0 AN: 518

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	0.063
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.055
DANN	Benign	0.81
DEOGEN2	Benign	0.00048	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00044	N
LIST_S2	Benign	0.033	T
M_CAP	Benign	0.00072	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-3.7
PrimateAI	Benign	0.19	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.021
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.030
MutPred		0.37		Loss of methylation at K76 (P = 3e-04)
MVP		0.030
MPC		0.074
ClinPred		0.061	T
GERP RS		-0.34
PromoterAI		0.014	Neutral
Varity_R		0.015
gMVP		0.023
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: rs1407887023; hg19: chr17-39254110; COSMIC: COSV61565257; COSMIC: COSV61565257;