9-136854228-C-T

Position:

• chr9-136854228-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000317446.7(MAMDC4):​c.688C>T​(p.Pro230Ser) 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. 13/21 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 ENST00000317446.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.455

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15994462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAMDC4	NM_206920.3	c.688C>T	p.Pro230Ser	missense_variant	7/27	ENST00000317446.7	NP_996803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAMDC4	ENST00000317446.7	c.688C>T	p.Pro230Ser	missense_variant	7/27	1	NM_206920.3	ENSP00000319388.2
MAMDC4	ENST00000485732.5	n.1124C>T		non_coding_transcript_exon_variant	7/25	1
MAMDC4	ENST00000445819.5	c.688C>T	p.Pro230Ser	missense_variant	7/29	5		ENSP00000411339.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2023

The c.688C>T (p.P230S) alteration is located in exon 7 (coding exon 7) of the MAMDC4 gene. This alteration results from a C to T substitution at nucleotide position 688, causing the proline (P) at amino acid position 230 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.77	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.22
Sift	Benign	0.18	T;T
Sift4G	Benign	0.65	T;T
Polyphen		0.037	B;.
Vest4		0.35
MutPred		0.44		Loss of catalytic residue at P230 (P = 0.0226);Loss of catalytic residue at P230 (P = 0.0226);
MVP		0.77
MPC		0.18
ClinPred		0.090	T
GERP RS		1.1
Varity_R		0.13
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr9-139748680;