9-136853566-C-T

Variant names:

• chr9-136853566-C-T
• NM_206920.3:c.350C>T

Variant summary

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

The NM_206920.3(MAMDC4):​c.350C>T​(p.Thr117Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAMDC4 NM_206920.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.347
• Publications: 0 publications found

Genes affected

MAMDC4 (HGNC:24083): (MAM domain containing 4) Predicted to be involved in protein transport. Predicted to be located in membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MAMDC4 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

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=0.28513756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206920.3. 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
	MAMDC4	NM_206920.3	MANE Select	c.350C>T	p.Thr117Ile	missense	Exon 4 of 27	NP_996803.2	Q6UXC1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAMDC4	ENST00000317446.7	TSL:1 MANE Select	c.350C>T	p.Thr117Ile	missense	Exon 4 of 27	ENSP00000319388.2	Q6UXC1-2
	MAMDC4	ENST00000485732.5	TSL:1	n.680C>T		non_coding_transcript_exon	Exon 5 of 25
	MAMDC4	ENST00000905523.1		c.353C>T	p.Thr118Ile	missense	Exon 4 of 29	ENSP00000575582.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.35
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.090
Sift	Benign	0.031	D
Sift4G	Benign	0.11	T
Polyphen		0.0090	B
Vest4		0.39
MutPred		0.72		Loss of disorder (P = 0.0418)
MVP		0.18
MPC		0.040
ClinPred		0.096	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.067
gMVP		0.50
Mutation Taster		=93/7	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

hg19: chr9-139748018;