rs867595

Variant names:

• chr9-70079625-T-G
• rs867595
• NM_153267.5:c.149-28586T>G

Variant summary

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

The ENST00000377182.5(MAMDC2):​c.149-28586T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,126 control chromosomes in the GnomAD database, including 3,982 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 0.19 (3982 hom., cov: 32)
• Consequence: MAMDC2 ENST00000377182.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 0 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377182.5. 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.149-28586T>G		intron	N/A	NP_694999.3
	MAMDC2	NM_001347990.2		c.149-28586T>G		intron	N/A	NP_001334919.1
	MAMDC2	NR_125850.1		n.766-28586T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMDC2	ENST00000377182.5	TSL:1 MANE Select	c.149-28586T>G		intron	N/A	ENSP00000366387.4
	MAMDC2-AS1	ENST00000625991.2	TSL:5	n.299+2349A>C		intron	N/A
	MAMDC2-AS1	ENST00000626773.2	TSL:5	n.198+7914A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28937 AN: 152008 Hom.: 3960 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.171

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

GnomAD4 genome AF: 0.191 AC: 29010 AN: 152126 Hom.: 3982 Cov.: 32 AF XY: 0.190 AC XY: 14100 AN XY: 74376

African (AFR) AF: 0.385 AC: 15975 AN: 41470

American (AMR) AF: 0.121 AC: 1847 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3472

East Asian (EAS) AF: 0.210 AC: 1087 AN: 5170

South Asian (SAS) AF: 0.229 AC: 1101 AN: 4818

European-Finnish (FIN) AF: 0.103 AC: 1096 AN: 10614

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6971 AN: 67988

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.135 Hom.: 1417

Bravo AF: 0.197

Asia WGS AF: 0.262 AC: 911 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		0.64
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: rs867595; hg19: chr9-72694541;