rs1356591875

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr21-30718716-C-A
• chr21-30718716-C-T

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>T​(p.Gly15Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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. G15D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP21-3 NM_001164435.1 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.13123038).

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>T	p.Gly15Val	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>T	p.Gly15Val	missense	Exon 1 of 1	ENSP00000404517.1	Q3LHN1
	ENSG00000295670	ENST00000731715.1		n.137+6801G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.89
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.38
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-9.0	D
REVEL	Benign	0.014
Sift4G	Pathogenic	0.0	D
Vest4		0.18
MutPred		0.39		Gain of sheet (P = 0.0043)
MVP		0.12
ClinPred		0.32	T
GERP RS		-0.76
PromoterAI		-0.0096	Neutral
Varity_R		0.19
gMVP		0.0030
Mutation Taster		=99/1	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;