rs760168004

Variant names:

• chr22-29731278-G-A
• rs760168004
• NM_001003692.2:c.460C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001003692.2(ZMAT5):​c.460C>T​(p.Arg154Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000474 in 1,520,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: ZMAT5 NM_001003692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.176
• Publications: 2 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15377474).

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.460C>T	p.Arg154Trp	missense	Exon 6 of 6	NP_001003692.1	Q9UDW3
	CABP7	NM_182527.3	MANE Select	c.*1709G>A		3_prime_UTR	Exon 5 of 5	NP_872333.1	Q86V35
	ZMAT5	NM_001318129.2		c.460C>T	p.Arg154Trp	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.460C>T	p.Arg154Trp	missense	Exon 6 of 6	ENSP00000344241.3	Q9UDW3
	CABP7	ENST00000216144.4	TSL:1 MANE Select	c.*1709G>A		3_prime_UTR	Exon 5 of 5	ENSP00000216144.3	Q86V35
	ZMAT5	ENST00000890523.1		c.460C>T	p.Arg154Trp	missense	Exon 6 of 6	ENSP00000560583.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 4 AN: 167526 AF XY: 0.0000428

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000734

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000236

Gnomad OTH exome AF: 0.000282

GnomAD4 exome AF: 0.0000482 AC: 66 AN: 1368262 Hom.: 0 Cov.: 30 AF XY: 0.0000575 AC XY: 39 AN XY: 678522

African (AFR) AF: 0.00 AC: 0 AN: 27078

American (AMR) AF: 0.000270 AC: 6 AN: 22262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23028

East Asian (EAS) AF: 0.00 AC: 0 AN: 32720

South Asian (SAS) AF: 0.0000143 AC: 1 AN: 69834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51902

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5506

European-Non Finnish (NFE) AF: 0.0000482 AC: 52 AN: 1079442

Other (OTH) AF: 0.000106 AC: 6 AN: 56490

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000395 Hom.: 0

Bravo AF: 0.0000680

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.015
Eigen_PC	Benign	-0.048
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.9	M
PhyloP100		-0.18
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.20
Sift	Benign	0.032	D
Sift4G	Benign	0.074	T
Polyphen		1.0	D
Vest4		0.17
MVP		0.092
ClinPred		0.70	D
GERP RS		3.1
Varity_R		0.091
gMVP		0.58
Mutation Taster		=83/17	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: rs760168004; hg19: chr22-30127267;