19-49200675-C-T

Variant summary

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

The NM_017636.4(TRPM4):​c.2843C>T​(p.Thr948Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TRPM4
NM_017636.4 missense

Scores

16
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.497
Variant links:
Genes affected
TRPM4 (HGNC:17993): (transient receptor potential cation channel subfamily M member 4) The protein encoded by this gene is a calcium-activated nonselective ion channel that mediates transport of monovalent cations across membranes, thereby depolarizing the membrane. The activity of the encoded protein increases with increasing intracellular calcium concentration, but this channel does not transport calcium. [provided by RefSeq, Mar 2016]

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/exons MANE Protein UniProt
TRPM4NM_017636.4 linkc.2843C>T p.Thr948Met missense_variant 19/25 ENST00000252826.10 NP_060106.2 Q8TD43-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRPM4ENST00000252826.10 linkc.2843C>T p.Thr948Met missense_variant 19/251 NM_017636.4 ENSP00000252826.4 Q8TD43-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152102
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250560
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135718
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:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461772
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727184
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152102
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.014
T
BayesDel_noAF
Benign
-0.22
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.65
D;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.62
D;D
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Uncertain
2.7
M;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-3.2
D;D
REVEL
Uncertain
0.29
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
D;D
Vest4
0.53
MutPred
0.36
Loss of catalytic residue at T948 (P = 0.1268);.;
MVP
0.72
MPC
1.0
ClinPred
0.96
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.59
gMVP
0.52

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: rs750756191; hg19: chr19-49703932; API