NM_001031628.2:c.106C>T

Variant names:

• chr12-51246760-G-A
• rs772997248
• NM_001031628.2:c.106C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031628.2(SMAGP):​c.106C>T​(p.Leu36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L36P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SMAGP NM_001031628.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41199535).

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.106C>T	p.Leu36Phe	missense	Exon 3 of 4	NP_001026798.1	Q0VAQ4
	SMAGP	NM_001033873.1		c.106C>T	p.Leu36Phe	missense	Exon 3 of 4	NP_001029045.1	Q0VAQ4
	DAZAP2	NM_001136269.2		c.*616G>A		downstream_gene	N/A	NP_001129741.1	Q15038-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMAGP	ENST00000603798.6	TSL:1 MANE Select	c.106C>T	p.Leu36Phe	missense	Exon 3 of 4	ENSP00000475068.1	Q0VAQ4
	SMAGP	ENST00000398453.7	TSL:1	c.106C>T	p.Leu36Phe	missense	Exon 3 of 4	ENSP00000381471.2	Q0VAQ4
	SMAGP	ENST00000380103.4	TSL:1	n.*111C>T		non_coding_transcript_exon	Exon 3 of 4	ENSP00000369446.4	A0A0A0MRX0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000462 AC: 1 AN: 216520 AF XY: 0.00000853

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: 0.0000496

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1434232 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 711828

African (AFR) AF: 0.00 AC: 0 AN: 32606

American (AMR) AF: 0.0000250 AC: 1 AN: 40050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25454

East Asian (EAS) AF: 0.00 AC: 0 AN: 38440

South Asian (SAS) AF: 0.00 AC: 0 AN: 81534

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098632

Other (OTH) AF: 0.00 AC: 0 AN: 59304

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.38	D
PhyloP100		2.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.41
Sift	Benign	0.032	D
Sift4G	Uncertain	0.057	T
Polyphen		0.99	D
Vest4		0.40
MutPred		0.28		Gain of sheet (P = 0.0827)
MVP		0.81
MPC		0.25
ClinPred		0.82	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.74
Mutation Taster		=75/25	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: rs772997248; hg19: chr12-51640544;