rs200201581

Variant names:

• chr21-30282599-C-G
• rs200201581
• NM_001085455.3:c.334G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-30282599-C-G
• chr21-30282599-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001085455.3(KRTAP24-1):​c.334G>C​(p.Val112Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000557 in 1,436,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V112I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: KRTAP24-1 NM_001085455.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 0 publications found

Genes affected

KRTAP24-1 (HGNC:33902): (keratin associated protein 24-1) Predicted to enable structural molecule activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033546954).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085455.3. 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
	KRTAP24-1	NM_001085455.3	MANE Select	c.334G>C	p.Val112Leu	missense	Exon 1 of 1	NP_001078924.1	Q3LI83

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRTAP24-1	ENST00000340345.6	TSL:6 MANE Select	c.334G>C	p.Val112Leu	missense	Exon 1 of 1	ENSP00000339238.4	Q3LI83

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000557 AC: 8 AN: 1436562 Hom.: 0 Cov.: 32 AF XY: 0.00000562 AC XY: 4 AN XY: 711710

African (AFR) AF: 0.00 AC: 0 AN: 32954

American (AMR) AF: 0.00 AC: 0 AN: 42844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23902

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 80568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 0.00000727 AC: 8 AN: 1099710

Other (OTH) AF: 0.00 AC: 0 AN: 59334

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.021
DANN	Benign	0.85
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-1.2
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.0030
Sift	Benign	0.21	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.021
MutPred		0.28		Loss of sheet (P = 0.0817)
MVP		0.088
MPC		0.013
ClinPred		0.048	T
GERP RS		-6.6
PromoterAI		-0.082	Neutral
Varity_R		0.049
gMVP		0.050
Mutation Taster		=98/2	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: rs200201581; hg19: chr21-31654917;