7-36357036-T-C

Variant names:

• chr7-36357036-T-C
• rs200592440
• NM_001199706.2:c.580A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001199706.2(MATCAP2):​c.580A>G​(p.Thr194Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000758 in 1,614,138 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (3 hom.)
• Consequence: MATCAP2 NM_001199706.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00
• Publications: 3 publications found

Genes affected

MATCAP2 (HGNC:22206): (microtubule associated tyrosine carboxypeptidase 2)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06540915).
• BS2: High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MATCAP2	NM_001199706.2	c.580A>G	p.Thr194Ala	missense_variant	Exon 2 of 7	ENST00000440378.6	NP_001186635.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MATCAP2	ENST00000440378.6	c.580A>G	p.Thr194Ala	missense_variant	Exon 2 of 7	1	NM_001199706.2	ENSP00000390837.1

Frequencies

GnomAD3 genomes AF: 0.000552 AC: 84 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000970

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000397 AC: 99 AN: 249446 AF XY: 0.000369

Gnomad AFR exome AF: 0.000323

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.000760

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000780 AC: 1140 AN: 1461854 Hom.: 3 Cov.: 33 AF XY: 0.000778 AC XY: 566 AN XY: 727236

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000981 AC: 1091 AN: 1111980

Other (OTH) AF: 0.000331 AC: 20 AN: 60392

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000470 AC XY: 35 AN XY: 74456

African (AFR) AF: 0.000337 AC: 14 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68018

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000566 Hom.: 0

Bravo AF: 0.000400

ESP6500AA AF: 0.00109 AC: 4

ESP6500EA AF: 0.000489 AC: 4

ExAC AF: 0.000381 AC: 46

EpiCase AF: 0.000545

EpiControl AF: 0.00101

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.733A>G (p.T245A) alteration is located in exon 3 (coding exon 3) of the KIAA0895 gene. This alteration results from a A to G substitution at nucleotide position 733, causing the threonine (T) at amino acid position 245 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.033	T;.;.;.;.;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.033
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.74	T;T;T;T;T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.065	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.;.;.;.;.;.
PhyloP100		4.0
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.18	T;T;T;T;T;T;D
Sift4G	Benign	0.28	T;T;T;T;T;T;.
Polyphen		0.33	B;B;B;.;.;B;.
Vest4		0.25
MVP		0.37
MPC		0.39
ClinPred		0.043	T
GERP RS		4.3
Varity_R		0.085
gMVP		0.16
Mutation Taster		=89/11	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: rs200592440; hg19: chr7-36396645;