rs782257584

Variant names:

• chr21-44654475-C-A
• NM_198698.1:c.140G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-44654475-C-A
• chr21-44654475-C-G
• chr21-44654475-C-T

Variant summary

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

The NM_198698.1(KRTAP12-4):​c.140G>T​(p.Arg47Leu) 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. R47Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KRTAP12-4 NM_198698.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

Genes affected

KRTAP12-4 (HGNC:20532): (keratin associated protein 12-4) Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TSPEAR (HGNC:1268): (thrombospondin type laminin G domain and EAR repeats) This gene encodes a protein that contains a N-terminal thrombospondin-type laminin G domain and several tandem arranged epilepsy-associated repeats (EARs). A mutation in this gene is the cause of autosomal recessive deafness-98. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

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=0.049869597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP12-4	NM_198698.1	c.140G>T	p.Arg47Leu	missense_variant	Exon 1 of 1	ENST00000391618.1	NP_941971.1
TSPEAR	NM_144991.3	c.82+56958G>T		intron_variant	Intron 1 of 11	ENST00000323084.9	NP_659428.2
TSPEAR	NM_001272037.2	c.-123+36070G>T		intron_variant	Intron 2 of 12		NP_001258966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP12-4	ENST00000391618.1	c.140G>T	p.Arg47Leu	missense_variant	Exon 1 of 1	6	NM_198698.1	ENSP00000375476.1
TSPEAR	ENST00000323084.9	c.82+56958G>T		intron_variant	Intron 1 of 11	1	NM_144991.3	ENSP00000321987.4
TSPEAR	ENST00000642437.1	n.*27+36070G>T		intron_variant	Intron 2 of 12			ENSP00000496535.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.027
DANN	Benign	0.69
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00091	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.00052	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.035
Sift	Benign	0.15	T
Sift4G	Benign	0.28	T
Polyphen		0.0070	B
Vest4		0.13
MutPred		0.28		Gain of catalytic residue at R47 (P = 0.0784);
MVP		0.27
MPC		0.016
ClinPred		0.089	T
GERP RS		-8.1
Varity_R		0.040
gMVP		0.058

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-46074392;