17-41140007-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030976.2(KRTAP4-6):​c.481C>G​(p.Arg161Gly) 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. 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. R161S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 47)
  • Exomes 𝑓: 0.0019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP4-6 NM_030976.2 missense
• Clinical Significance: Not reported in ClinVar
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0067867935).

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>G	p.Arg161Gly	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>G	p.Arg161Gly	missense	Exon 1 of 1	ENSP00000328270.5	Q9BYQ5

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 183 AN: 152092 Hom.: 0 Cov.: 47

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00209

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00114 AC: 281 AN: 246574 AF XY: 0.00119

Gnomad AFR exome AF: 0.000192

Gnomad AMR exome AF: 0.000530

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000372

Gnomad NFE exome AF: 0.00206

Gnomad OTH exome AF: 0.00182

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00193 AC: 2793 AN: 1444578 Hom.: 0 Cov.: 305 AF XY: 0.00194 AC XY: 1395 AN XY: 718736

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

African (AFR) AF: 0.000210 AC: 7 AN: 33334

American (AMR) AF: 0.000793 AC: 35 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25950

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.000514 AC: 44 AN: 85636

European-Finnish (FIN) AF: 0.000621 AC: 33 AN: 53166

Middle Eastern (MID) AF: 0.000710 AC: 4 AN: 5636

European-Non Finnish (NFE) AF: 0.00234 AC: 2567 AN: 1097302

Other (OTH) AF: 0.00172 AC: 103 AN: 59820

⚠️ 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: 0.00120 AC: 183 AN: 152210 Hom.: 0 Cov.: 47 AF XY: 0.00112 AC XY: 83 AN XY: 74432

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

African (AFR) AF: 0.000385 AC: 16 AN: 41574

American (AMR) AF: 0.00118 AC: 18 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00209 AC: 142 AN: 67934

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

⚠️ 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: 0.00161 Hom.: 0

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00311 AC: 12

ExAC AF: 0.00149 AC: 181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.2
DANN	Benign	0.68
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.086	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.0068	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L
PhyloP100		-3.6
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.046
Sift	Benign	0.11	T
Sift4G	Benign	0.17	T
Vest4		0.11
MutPred		0.21		Gain of glycosylation at S158 (P = 0.0507)
MVP		0.067
MPC		0.067
ClinPred		0.019	T
GERP RS		-7.1
PromoterAI		0.0064	Neutral
Varity_R		0.071
gMVP		0.16
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;