rs368691129

Variant names:

• chr21-30755308-G-A
• rs368691129
• NM_181619.2:c.71C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-30755308-G-A
• chr21-30755308-G-C
• chr21-30755308-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_181619.2(KRTAP21-1):​c.71C>T​(p.Ser24Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,652 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S24C) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: KRTAP21-1 NM_181619.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

KRTAP21-1 (HGNC:18945): (keratin associated protein 21-1) Predicted to be involved in hair follicle development. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044941634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP21-1	NM_181619.2	c.71C>T	p.Ser24Phe	missense_variant	Exon 1 of 1	ENST00000335093.5	NP_853650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP21-1	ENST00000335093.5	c.71C>T	p.Ser24Phe	missense_variant	Exon 1 of 1	6	NM_181619.2	ENSP00000335566.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151652 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151652 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74058

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.3
DANN	Benign	0.30
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.051
Sift	Benign	0.71	T
Sift4G	Benign	0.66	T
Polyphen		0.0020	B
Vest4		0.30
MutPred		0.26		Loss of glycosylation at S24 (P = 8e-04);
MVP		0.11
MPC		0.028
ClinPred		0.023	T
GERP RS		-2.3
Varity_R		0.030
gMVP		0.017

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

Publications

LitVar

Other links and lift over

dbSNP: rs368691129; hg19: chr21-32127626;