12-51269247-C-G

Variant names:

• chr12-51269247-C-G
• rs371385707
• NM_001031628.2:c.32G>C

Variant summary

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

The NM_001031628.2(SMAGP):​c.32G>C​(p.Arg11Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. R11I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMAGP NM_001031628.2 missense, splice_region
• Scores: Splicing: ADA: 0.00003175
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 0 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: 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=0.04218179).

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.32G>C	p.Arg11Thr	missense splice_region	Exon 2 of 4	NP_001026798.1	Q0VAQ4
	SMAGP	NM_001033873.1		c.32G>C	p.Arg11Thr	missense splice_region	Exon 2 of 4	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.32G>C	p.Arg11Thr	missense splice_region	Exon 2 of 4	ENSP00000475068.1	Q0VAQ4
	SMAGP	ENST00000398453.7	TSL:1	c.32G>C	p.Arg11Thr	missense splice_region	Exon 2 of 4	ENSP00000381471.2	Q0VAQ4
	SMAGP	ENST00000380103.4	TSL:1	n.32G>C		splice_region non_coding_transcript_exon	Exon 1 of 4	ENSP00000369446.4	A0A0A0MRX0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249258 AF XY: 0.00000740

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461590 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727092

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111790

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.0
DANN	Benign	0.20
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.16
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.0090
Sift	Benign	0.31	T
Sift4G	Benign	0.54	T
Polyphen		0.0070	B
Vest4		0.13
MutPred		0.22		Gain of glycosylation at R11 (P = 0.0029)
MVP		0.040
MPC		0.043
ClinPred		0.016	T
GERP RS		-0.99
Varity_R		0.054
gMVP		0.42
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs371385707; hg19: chr12-51663031;