9-97551511-C-T

Variant names:

• chr9-97551511-C-T
• rs4743106
• NM_003275.4:c.278-1770C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003275.4(TMOD1):​c.278-1770C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,074 control chromosomes in the GnomAD database, including 46,515 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.78 (46515 hom., cov: 32)
• Consequence: TMOD1 NM_003275.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• Publications: 2 publications found

Genes affected

TMOD1 (HGNC:11871): (tropomodulin 1) This gene encodes a member of the tropomodulin family. The encoded protein is an actin-capping protein that regulates tropomyosin by binding to its N-terminus, inhibiting depolymerization and elongation of the pointed end of actin filaments and thereby influencing the structure of the erythrocyte membrane skeleton. Multiple transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Oct 2009]

TMOD1 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003275.4. 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
	TMOD1	NM_003275.4	MANE Select	c.278-1770C>T		intron	N/A	NP_003266.1	P28289-1
	TMOD1	NM_001166116.2		c.278-1770C>T		intron	N/A	NP_001159588.1	P28289-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMOD1	ENST00000259365.9	TSL:1 MANE Select	c.278-1770C>T		intron	N/A	ENSP00000259365.3	P28289-1
	TMOD1	ENST00000395211.6	TSL:1	c.278-1770C>T		intron	N/A	ENSP00000378637.2	P28289-1
	TMOD1	ENST00000950655.1		c.401-1770C>T		intron	N/A	ENSP00000620714.1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118685 AN: 151956 Hom.: 46485 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.764

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.781 AC: 118771 AN: 152074 Hom.: 46515 Cov.: 32 AF XY: 0.782 AC XY: 58116 AN XY: 74318

African (AFR) AF: 0.748 AC: 31018 AN: 41444

American (AMR) AF: 0.717 AC: 10950 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2643 AN: 3470

East Asian (EAS) AF: 0.741 AC: 3832 AN: 5172

South Asian (SAS) AF: 0.841 AC: 4051 AN: 4818

European-Finnish (FIN) AF: 0.840 AC: 8898 AN: 10594

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54692 AN: 67990

Other (OTH) AF: 0.766 AC: 1621 AN: 2116

Alfa AF: 0.789 Hom.: 113973

Bravo AF: 0.767

Asia WGS AF: 0.796 AC: 2769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.64
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs4743106; hg19: chr9-100313793;