chr9-70126401-C-G

Position:

• chr9-70126401-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153267.5(MAMDC2):​c.886C>G​(p.Pro296Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAMDC2 NM_153267.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAMDC2	NM_153267.5	c.886C>G	p.Pro296Ala	missense_variant	6/14	ENST00000377182.5
MAMDC2	NM_001347990.2	c.886C>G	p.Pro296Ala	missense_variant	6/12
MAMDC2	NR_125850.1	n.1503C>G		non_coding_transcript_exon_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAMDC2	ENST00000377182.5	c.886C>G	p.Pro296Ala	missense_variant	6/14	1	NM_153267.5	P1
MAMDC2-AS1	ENST00000591368.5	n.409-12541G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460922 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726768

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0073	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.33
Sift	Benign	0.085	T
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.42		Loss of loop (P = 0.0804);
MVP		0.58
MPC		0.44
ClinPred		0.94	D
GERP RS		6.0
Varity_R		0.33
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-72741317;