9-70083123-G-C

Variant names:

• chr9-70083123-G-C
• rs3015182
• NM_153267.5:c.149-25088G>C

Variant summary

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

The NM_153267.5(MAMDC2):​c.149-25088G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,062 control chromosomes in the GnomAD database, including 3,656 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 0.18 (3656 hom., cov: 33)
• Consequence: MAMDC2 NM_153267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889
• Publications: 3 publications found

Genes affected

MAMDC2 (HGNC:23673): (MAM domain containing 2) Predicted to enable glycosaminoglycan binding activity. Predicted to act upstream of or within peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

MAMDC2-AS1 (HGNC:48719): (MAMDC2 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153267.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMDC2	NM_153267.5	MANE Select	c.149-25088G>C		intron	N/A	NP_694999.3
	MAMDC2	NM_001347990.2		c.149-25088G>C		intron	N/A	NP_001334919.1
	MAMDC2	NR_125850.1		n.766-25088G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMDC2	ENST00000377182.5	TSL:1 MANE Select	c.149-25088G>C		intron	N/A	ENSP00000366387.4
	MAMDC2-AS1	ENST00000625991.2	TSL:5	n.199-1049C>G		intron	N/A
	MAMDC2-AS1	ENST00000626529.2	TSL:5	n.199-223C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28052 AN: 151944 Hom.: 3635 Cov.: 33

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.185 AC: 28124 AN: 152062 Hom.: 3656 Cov.: 33 AF XY: 0.184 AC XY: 13676 AN XY: 74362

African (AFR) AF: 0.367 AC: 15200 AN: 41466

American (AMR) AF: 0.117 AC: 1792 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1076 AN: 5148

South Asian (SAS) AF: 0.227 AC: 1096 AN: 4818

European-Finnish (FIN) AF: 0.103 AC: 1088 AN: 10602

Middle Eastern (MID) AF: 0.171 AC: 50 AN: 292

European-Non Finnish (NFE) AF: 0.102 AC: 6951 AN: 67968

Other (OTH) AF: 0.171 AC: 362 AN: 2112

Alfa AF: 0.132 Hom.: 255

Bravo AF: 0.190

Asia WGS AF: 0.261 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.70
DANN	Benign	0.71
PhyloP100		-0.89
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

Other links and lift over

dbSNP: rs3015182; hg19: chr9-72698039;