rs753490829

Variant names:

• chr21-30282701-G-A
• NM_001085455.3:c.232C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-30282701-G-A
• chr21-30282701-G-T

Variant summary

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

The NM_001085455.3(KRTAP24-1):​c.232C>T​(p.Pro78Ser) 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. 14/21 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. P78T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KRTAP24-1 NM_001085455.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538

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

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=0.040618062).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP24-1	NM_001085455.3	c.232C>T	p.Pro78Ser	missense_variant	Exon 1 of 1	ENST00000340345.6	NP_001078924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP24-1	ENST00000340345.6	c.232C>T	p.Pro78Ser	missense_variant	Exon 1 of 1	6	NM_001085455.3	ENSP00000339238.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.35
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.025
Sift	Benign	0.81	T
Sift4G	Benign	0.15	T
Polyphen		0.0070	B
Vest4		0.12
MutPred		0.30		Loss of glycosylation at S75 (P = 0.0664);
MVP		0.21
MPC		0.087
ClinPred		0.099	T
GERP RS		0.90
Varity_R		0.059
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr21-31655019; COSMIC: COSV100447521;