22-29731317-C-G

Variant names:

• chr22-29731317-C-G
• rs765805169
• NM_001003692.2:c.421G>C

Variant summary

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

The NM_001003692.2(ZMAT5):​c.421G>C​(p.Val141Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000392 in 1,531,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. V141M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: ZMAT5 NM_001003692.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 0 publications found

Genes affected

ZMAT5 (HGNC:28046): (zinc finger matrin-type 5) Predicted to enable zinc ion binding activity. Predicted to be involved in RNA splicing. Located in nucleoplasm. Part of U12-type spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

CABP7 (HGNC:20834): (calcium binding protein 7) Predicted to enable calcium ion binding activity. Located in trans-Golgi network membrane. [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=0.017976493).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003692.2. 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
	ZMAT5	NM_001003692.2	MANE Select	c.421G>C	p.Val141Leu	missense	Exon 6 of 6	NP_001003692.1	Q9UDW3
	CABP7	NM_182527.3	MANE Select	c.*1748C>G		3_prime_UTR	Exon 5 of 5	NP_872333.1	Q86V35
	ZMAT5	NM_001318129.2		c.421G>C	p.Val141Leu	missense	Exon 6 of 6	NP_001305058.1	Q9UDW3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMAT5	ENST00000344318.4	TSL:1 MANE Select	c.421G>C	p.Val141Leu	missense	Exon 6 of 6	ENSP00000344241.3	Q9UDW3
	CABP7	ENST00000216144.4	TSL:1 MANE Select	c.*1748C>G		3_prime_UTR	Exon 5 of 5	ENSP00000216144.3	Q86V35
	ZMAT5	ENST00000890523.1		c.421G>C	p.Val141Leu	missense	Exon 6 of 6	ENSP00000560583.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152066 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000564 AC: 1 AN: 177198 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000113

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000363 AC: 5 AN: 1379294 Hom.: 0 Cov.: 30 AF XY: 0.00000292 AC XY: 2 AN XY: 684274

African (AFR) AF: 0.00 AC: 0 AN: 27878

American (AMR) AF: 0.00 AC: 0 AN: 25636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23500

East Asian (EAS) AF: 0.00 AC: 0 AN: 33040

South Asian (SAS) AF: 0.00 AC: 0 AN: 71800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.00000462 AC: 5 AN: 1082834

Other (OTH) AF: 0.00 AC: 0 AN: 56976

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152066 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74272

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.52
DANN	Benign	0.65
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.37
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.0080
Sift	Benign	0.90	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.18		Gain of catalytic residue at V141 (P = 0.074)
MVP		0.014
ClinPred		0.0087	T
GERP RS		-7.4
Varity_R		0.029
gMVP		0.32
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs765805169; hg19: chr22-30127306;