chr9-136853324-C-T

Variant names:

• chr9-136853324-C-T
• NM_206920.3:c.194C>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.194C>T​(p.Ala65Val) 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. 15/22 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: 1.75
• 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=0.3621583).

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.194C>T	p.Ala65Val	missense	Exon 3 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.194C>T	p.Ala65Val	missense	Exon 3 of 27	ENSP00000319388.2	Q6UXC1-2
	MAMDC4	ENST00000485732.5	TSL:1	n.438C>T		non_coding_transcript_exon	Exon 5 of 25
	MAMDC4	ENST00000905523.1		c.197C>T	p.Ala66Val	missense	Exon 3 of 29	ENSP00000575582.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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	0.081
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.7
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.058
Sift	Benign	0.14	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.55		Loss of disorder (P = 0.1019)
MVP		0.22
MPC		0.023
ClinPred		0.12	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.053
gMVP		0.15
Mutation Taster		=95/5	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: chr9-139747776;