chr9-70126363-A-G

Variant names:

• chr9-70126363-A-G
• rs1174165233
• NM_153267.5:c.848A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_153267.5(MAMDC2):​c.848A>G​(p.Asn283Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAMDC2 NM_153267.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.505
• 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: 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=0.071763545).
• BP6: Variant 9-70126363-A-G is Benign according to our data. Variant chr9-70126363-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2393647.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMDC2	NM_153267.5	MANE Select	c.848A>G	p.Asn283Ser	missense	Exon 6 of 14	NP_694999.3
	MAMDC2	NM_001347990.2		c.848A>G	p.Asn283Ser	missense	Exon 6 of 12	NP_001334919.1
	MAMDC2	NR_125850.1		n.1465A>G		non_coding_transcript_exon	Exon 6 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMDC2	ENST00000377182.5	TSL:1 MANE Select	c.848A>G	p.Asn283Ser	missense	Exon 6 of 14	ENSP00000366387.4	Q7Z304-1
	MAMDC2	ENST00000864380.1		c.848A>G	p.Asn283Ser	missense	Exon 6 of 15	ENSP00000534439.1
	MAMDC2	ENST00000911415.1		c.848A>G	p.Asn283Ser	missense	Exon 6 of 13	ENSP00000581474.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461774 Hom.: 0 Cov.: 45 AF XY: 0.00000275 AC XY: 2 AN XY: 727190

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.13
DANN	Benign	0.53
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-0.51
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.055
Sift	Benign	0.50	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.088
MutPred		0.66		Gain of glycosylation at N283 (P = 0.0169)
MVP		0.16
MPC		0.090
ClinPred		0.041	T
GERP RS		-0.063
Varity_R		0.036
gMVP		0.21
Mutation Taster		=92/8	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: rs1174165233; hg19: chr9-72741279;