rs199737998

Variant names:

• chr21-30813040-C-A
• NM_175857.4:c.181G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-30813040-C-A
• chr21-30813040-C-T

Variant summary

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

The NM_175857.4(KRTAP8-1):​c.181G>T​(p.Ala61Ser) 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. 14/19 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. A61T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP8-1 NM_175857.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

Genes affected

KRTAP8-1 (HGNC:18935): (keratin associated protein 8-1) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06834537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP8-1	NM_175857.4	c.181G>T	p.Ala61Ser	missense_variant	Exon 1 of 1	ENST00000329621.6	NP_787053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP8-1	ENST00000329621.6	c.181G>T	p.Ala61Ser	missense_variant	Exon 1 of 1	6	NM_175857.4	ENSP00000332805.4

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	0.073
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.49
DANN	Benign	0.71
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.044
Sift	Benign	0.17	T
Sift4G	Benign	0.33	T
Polyphen		0.042	B
Vest4		0.17
MutPred		0.17		Gain of glycosylation at A61 (P = 0.0092);
MVP		0.014
MPC		1.0
ClinPred		0.23	T
GERP RS		0.061
Varity_R		0.10
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-32185358; COSMIC: COSV61598429;