9-136853568-C-T

Variant names:

• chr9-136853568-C-T
• rs576315462
• NM_206920.3:c.352C>T

Variant summary

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

The NM_206920.3(MAMDC4):​c.352C>T​(p.His118Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,268 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H118D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MAMDC4 NM_206920.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.22

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]

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 rank	MANE	Protein	UniProt
MAMDC4	NM_206920.3	c.352C>T	p.His118Tyr	missense_variant	Exon 4 of 27	ENST00000317446.7	NP_996803.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAMDC4	ENST00000317446.7	c.352C>T	p.His118Tyr	missense_variant	Exon 4 of 27	1	NM_206920.3	ENSP00000319388.2
MAMDC4	ENST00000485732.5	n.682C>T		non_coding_transcript_exon_variant	Exon 5 of 25	1
MAMDC4	ENST00000445819.5	c.352C>T	p.His118Tyr	missense_variant	Exon 4 of 29	5		ENSP00000411339.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249110 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135352

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460268 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726434

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	.;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Benign	0.096
Sift	Benign	0.088	T;T
Sift4G	Uncertain	0.047	D;D
Polyphen		1.0	D;.
Vest4		0.57
MutPred		0.50		Loss of disorder (P = 0.0662);Loss of disorder (P = 0.0662);
MVP		0.30
MPC		0.20
ClinPred		0.46	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs576315462; hg19: chr9-139748020;