rs774077198

Variant names:

• chr21-30718647-C-A
• NM_001164435.1:c.113G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-30718647-C-A
• chr21-30718647-C-T

Variant summary

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

The NM_001164435.1(KRTAP21-3):​c.113G>T​(p.Cys38Phe) 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. 13/18 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. C38G) 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: -0.177

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]

LOC105372773 (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=0.15385601).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP21-3	NM_001164435.1	c.113G>T	p.Cys38Phe	missense_variant	Exon 1 of 1	ENST00000444335.1	NP_001157907.1
LOC105372773	XR_937655.3	n.407+3453G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP21-3	ENST00000444335.1	c.113G>T	p.Cys38Phe	missense_variant	Exon 1 of 1	6	NM_001164435.1	ENSP00000404517.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.3
DANN	Benign	0.77
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.061	N
M_CAP	Benign	0.00044	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-11	D
REVEL	Benign	0.078
Sift4G	Pathogenic	0.0	D
Vest4		0.23
MutPred		0.27		Gain of sheet (P = 0.0827);
MVP		0.061
ClinPred		0.39	T
GERP RS		-3.2
Varity_R		0.29
gMVP		0.0041

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-32090965;