rs7305016

Variant names:

• chr12-51248759-A-G
• rs7305016
• NM_001031628.2:c.35-1928T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031628.2(SMAGP):​c.35-1928T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,908 control chromosomes in the GnomAD database, including 22,421 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22421 hom., cov: 30)
• Consequence: SMAGP NM_001031628.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232
• Publications: 8 publications found

Genes affected

SMAGP (HGNC:26918): (small cell adhesion glycoprotein) Located in cell junction; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

DAZAP2 (HGNC:2684): (DAZ associated protein 2) This gene encodes a proline-rich protein which interacts with the deleted in azoospermia (DAZ) and the deleted in azoospermia-like gene through the DAZ-like repeats. This protein also interacts with the transforming growth factor-beta signaling molecule SARA (Smad anchor for receptor activation), eukaryotic initiation factor 4G, and an E3 ubiquitinase that regulates its stability in splicing factor containing nuclear speckles. The encoded protein may function in various biological and pathological processes including spermatogenesis, cell signaling and transcription regulation, formation of stress granules during translation arrest, RNA splicing, and pathogenesis of multiple myeloma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031628.2. 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
	SMAGP	NM_001031628.2	MANE Select	c.35-1928T>C		intron	N/A	NP_001026798.1	Q0VAQ4
	SMAGP	NM_001033873.1		c.35-1928T>C		intron	N/A	NP_001029045.1	Q0VAQ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAGP	ENST00000603798.6	TSL:1 MANE Select	c.35-1928T>C		intron	N/A	ENSP00000475068.1	Q0VAQ4
	SMAGP	ENST00000398453.7	TSL:1	c.35-1928T>C		intron	N/A	ENSP00000381471.2	Q0VAQ4
	SMAGP	ENST00000380103.4	TSL:1	n.*40-1928T>C		intron	N/A	ENSP00000369446.4	A0A0A0MRX0

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80177 AN: 151790 Hom.: 22413 Cov.: 30

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.528 AC: 80213 AN: 151908 Hom.: 22421 Cov.: 30 AF XY: 0.525 AC XY: 38991 AN XY: 74240

African (AFR) AF: 0.341 AC: 14137 AN: 41420

American (AMR) AF: 0.525 AC: 8013 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2225 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1914 AN: 5154

South Asian (SAS) AF: 0.609 AC: 2928 AN: 4808

European-Finnish (FIN) AF: 0.554 AC: 5844 AN: 10558

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43157 AN: 67936

Other (OTH) AF: 0.572 AC: 1204 AN: 2104

Alfa AF: 0.604 Hom.: 45856

Bravo AF: 0.513

Asia WGS AF: 0.492 AC: 1713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7305016;

hg19: chr12-51642543;