NM_001005922.1:c.342A>C

Variant names:

• chr11-1584908-T-G
• rs80025267
• NM_001005922.1:c.342A>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001005922.1(KRTAP5-1):​c.342A>C​(p.Gly114Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.029 (1 hom., cov: 0)
  • Exomes 𝑓: 0.011 (95 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRTAP5-1 NM_001005922.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 3 publications found

Genes affected

KRTAP5-1 (HGNC:23596): (keratin associated protein 5-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

KRTAP5-AS1 (HGNC:27877): (KRTAP5-1/KRTAP5-2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-2.04 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005922.1. 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
	KRTAP5-1	NM_001005922.1	MANE Select	c.342A>C	p.Gly114Gly	synonymous	Exon 1 of 1	NP_001005922.1	Q6L8H4
	KRTAP5-AS1	NR_021489.2		n.328+11840T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP5-1	ENST00000382171.2	TSL:6 MANE Select	c.342A>C	p.Gly114Gly	synonymous	Exon 1 of 1	ENSP00000371606.2	Q6L8H4
	KRTAP5-AS1	ENST00000424148.1	TSL:2	n.328+11840T>G		intron	N/A
	KRTAP5-AS1	ENST00000524947.1	TSL:4	n.235-12340T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 138 AN: 4630 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.0313

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.0250

Gnomad EAS AF: 0.0238

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0348

Gnomad OTH AF: 0.0500

GnomAD2 exomes AF: 0.0104 AC: 2089 AN: 200984 AF XY: 0.0105

Gnomad AFR exome AF: 0.00459

Gnomad AMR exome AF: 0.00980

Gnomad ASJ exome AF: 0.0154

Gnomad EAS exome AF: 0.00438

Gnomad FIN exome AF: 0.00744

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.0127

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0108 AC: 2695 AN: 249910 Hom.: 95 Cov.: 0 AF XY: 0.0108 AC XY: 1326 AN XY: 122298

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

African (AFR) AF: 0.0129 AC: 65 AN: 5030

American (AMR) AF: 0.0139 AC: 124 AN: 8924

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 63 AN: 5426

East Asian (EAS) AF: 0.00534 AC: 33 AN: 6176

South Asian (SAS) AF: 0.0109 AC: 155 AN: 14260

European-Finnish (FIN) AF: 0.0296 AC: 152 AN: 5136

Middle Eastern (MID) AF: 0.00911 AC: 7 AN: 768

European-Non Finnish (NFE) AF: 0.0102 AC: 1979 AN: 193952

Other (OTH) AF: 0.0114 AC: 117 AN: 10238

⚠️ 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: 0.0294 AC: 137 AN: 4654 Hom.: 1 Cov.: 0 AF XY: 0.0285 AC XY: 64 AN XY: 2246

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

African (AFR) AF: 0.0242 AC: 23 AN: 950

American (AMR) AF: 0.0109 AC: 4 AN: 366

Ashkenazi Jewish (ASJ) AF: 0.0250 AC: 4 AN: 160

East Asian (EAS) AF: 0.0190 AC: 4 AN: 210

South Asian (SAS) AF: 0.0139 AC: 2 AN: 144

European-Finnish (FIN) AF: 0.0407 AC: 7 AN: 172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0348 AC: 89 AN: 2554

Other (OTH) AF: 0.0484 AC: 3 AN: 62

⚠️ 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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.35
PhyloP100		-2.0
PromoterAI		-0.0032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs80025267; hg19: chr11-1606138; COSMIC: COSV66298770;