9-136853568-C-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

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.22
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
MAMDC4NM_206920.3 linkc.352C>T p.His118Tyr missense_variant Exon 4 of 27 ENST00000317446.7 NP_996803.2 Q6UXC1-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAMDC4ENST00000317446.7 linkc.352C>T p.His118Tyr missense_variant Exon 4 of 27 1 NM_206920.3 ENSP00000319388.2 Q6UXC1-2
MAMDC4ENST00000485732.5 linkn.682C>T non_coding_transcript_exon_variant Exon 5 of 25 1
MAMDC4ENST00000445819.5 linkc.352C>T p.His118Tyr missense_variant Exon 4 of 29 5 ENSP00000411339.1 Q6UXC1-1

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
show subpopulations
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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs576315462; hg19: chr9-139748020; API