chr21-30718716-C-T

Variant names:

• chr21-30718716-C-T
• rs1356591875
• NM_001164435.1:c.44G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164435.1(KRTAP21-3):​c.44G>A​(p.Gly15Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KRTAP21-3 NM_001164435.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.378
• Publications: 0 publications found

Genes affected

KRTAP21-3 (HGNC:34216): (keratin associated protein 21-3) Predicted to be located in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000295670 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10980868).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164435.1. 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
	KRTAP21-3	NM_001164435.1	MANE Select	c.44G>A	p.Gly15Asp	missense	Exon 1 of 1	NP_001157907.1	Q3LHN1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP21-3	ENST00000444335.1	TSL:6 MANE Select	c.44G>A	p.Gly15Asp	missense	Exon 1 of 1	ENSP00000404517.1	Q3LHN1
	ENSG00000295670	ENST00000731715.1		n.137+6801G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000678 AC: 1 AN: 147462 AF XY: 0.0000128

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000461

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 AF: 7.19e-7 AC: 1 AN: 1391250 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 685942

African (AFR) AF: 0.00 AC: 0 AN: 31128

American (AMR) AF: 0.0000295 AC: 1 AN: 33860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25040

East Asian (EAS) AF: 0.00 AC: 0 AN: 35196

South Asian (SAS) AF: 0.00 AC: 0 AN: 77324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076114

Other (OTH) AF: 0.00 AC: 0 AN: 57710

GnomAD4 genome Cov.: 32

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	0.28
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.8
DANN	Benign	0.87
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.20	N
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.38
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.045
Sift4G	Pathogenic	0.0	D
Vest4		0.19
MutPred		0.22		Loss of catalytic residue at G13 (P = 0.1026)
MVP		0.030
ClinPred		0.16	T
GERP RS		-0.76
PromoterAI		-0.020	Neutral
Varity_R		0.27
gMVP		0.0029
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1356591875; hg19: chr21-32091034;