chr21-30642962-T-C

Variant names:

• chr21-30642962-T-C
• rs984084816
• NM_001128077.1:c.74T>C

Variant summary

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

The NM_001128077.1(KRTAP20-3):​c.74T>C​(p.Phe25Ser) 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. 12/20 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. F25Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP20-3 NM_001128077.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 0 publications found

Genes affected

KRTAP20-3 (HGNC:34001): (keratin associated protein 20-3) Predicted to be located in intermediate filament. [provided by Alliance of Genome Resources, Apr 2022]

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=0.22111017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128077.1. 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
	KRTAP20-3	NM_001128077.1	MANE Select	c.74T>C	p.Phe25Ser	missense	Exon 1 of 1	NP_001121549.1	Q3LI60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP20-3	ENST00000382826.2	TSL:6 MANE Select	c.74T>C	p.Phe25Ser	missense	Exon 1 of 1	ENSP00000372276.2	Q3LI60

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000633 AC: 1 AN: 157962 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000163

Gnomad OTH exome AF: 0.00

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	Pathogenic	0.77
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.47
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.015	N
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.19
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.031
Sift4G	Benign	0.11	T
Polyphen		0.26	B
Vest4		0.58
MutPred		0.31		Gain of glycosylation at F25 (P = 0.0023)
MVP		0.076
ClinPred		0.14	T
GERP RS		-8.4
PromoterAI		-0.0053	Neutral
Varity_R		0.29
gMVP		0.43
Mutation Taster		=99/1	polymorphism

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: rs984084816; hg19: chr21-32015281;