21-30430406-G-C

Variant names:

• chr21-30430406-G-C
• rs139303515
• NM_181600.3:c.131G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181600.3(KRTAP13-4):​c.131G>C​(p.Arg44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: KRTAP13-4 NM_181600.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

Genes affected

KRTAP13-4 (HGNC:18926): (keratin associated protein 13-4) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LOC105372772 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11038399).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP13-4	NM_181600.3	c.131G>C	p.Arg44Pro	missense_variant	Exon 1 of 1	ENST00000334068.4	NP_853631.1
LOC105372772	XR_937653.3	n.196-37046C>G		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP13-4	ENST00000334068.4	c.131G>C	p.Arg44Pro	missense_variant	Exon 1 of 1	6	NM_181600.3	ENSP00000334834.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152120 Hom.: 0 Cov.: 33

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000239 AC: 6 AN: 251400 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135866

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 43 AN: 1461890 Hom.: 0 Cov.: 30 AF XY: 0.0000289 AC XY: 21 AN XY: 727248

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152120 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74304

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00000515 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.075	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.035
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.071	T
Polyphen		0.023	B
Vest4		0.092
MutPred		0.52		Loss of solvent accessibility (P = 0.0299);
MVP		0.12
MPC		0.047
ClinPred		0.11	T
GERP RS		2.1
Varity_R		0.19
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139303515; hg19: chr21-31802724;