rs776412887

Variant names:

• chr17-41140007-G-A
• rs776412887
• NM_030976.2:c.481C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-41140007-G-A
• chr17-41140007-G-T
• chr17-41140007-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_030976.2(KRTAP4-6):​c.481C>T​(p.Arg161Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000705 in 1,446,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R161S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 47)
  • Exomes 𝑓: 0.000071 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-6 NM_030976.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.58
• Publications: 2 publications found

Genes affected

KRTAP4-6 (HGNC:18909): (keratin associated protein 4-6) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0825496).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030976.2. 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
	KRTAP4-6	NM_030976.2	MANE Select	c.481C>T	p.Arg161Cys	missense	Exon 1 of 1	NP_112238.1	Q9BYQ5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP4-6	ENST00000345847.5	TSL:6 MANE Select	c.481C>T	p.Arg161Cys	missense	Exon 1 of 1	ENSP00000328270.5	Q9BYQ5

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152212 Hom.: 0 Cov.: 47

Gnomad AFR AF: 0.0000724

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000568 AC: 14 AN: 246574 AF XY: 0.0000599

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000554

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000630

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.0000705 AC: 102 AN: 1446220 Hom.: 0 Cov.: 305 AF XY: 0.0000750 AC XY: 54 AN XY: 719560

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

African (AFR) AF: 0.000150 AC: 5 AN: 33338

American (AMR) AF: 0.0000227 AC: 1 AN: 44138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39612

South Asian (SAS) AF: 0.0000584 AC: 5 AN: 85654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53178

Middle Eastern (MID) AF: 0.00106 AC: 6 AN: 5638

European-Non Finnish (NFE) AF: 0.0000701 AC: 77 AN: 1098848

Other (OTH) AF: 0.000100 AC: 6 AN: 59862

⚠️ 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: 0.0000394 AC: 6 AN: 152212 Hom.: 0 Cov.: 47 AF XY: 0.0000538 AC XY: 4 AN XY: 74360

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

African (AFR) AF: 0.0000724 AC: 3 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00163186), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000107 Hom.: 0

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ExAC AF: 0.0000742 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.19
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.1
DANN	Benign	0.89
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-3.6
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.11
Sift	Benign	0.032	D
Sift4G	Uncertain	0.044	D
Vest4		0.10
MutPred		0.19		Gain of glycosylation at S158 (P = 0.0735)
MVP		0.067
MPC		0.071
ClinPred		0.14	T
GERP RS		-7.1
PromoterAI		-0.0018	Neutral
Varity_R		0.10
gMVP		0.15
Mutation Taster		=99/1	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: rs776412887; hg19: chr17-39296259;