9-97553948-C-T

Variant names:

• chr9-97553948-C-T
• rs1475545
• NM_003275.4:c.397+548C>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.397+548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 151,802 control chromosomes in the GnomAD database, including 22,043 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 0.54 (22043 hom., cov: 30)
• Consequence: TMOD1 NM_003275.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 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.397+548C>T		intron	N/A	NP_003266.1	P28289-1
	TMOD1	NM_001166116.2		c.397+548C>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.397+548C>T		intron	N/A	ENSP00000259365.3	P28289-1
	TMOD1	ENST00000395211.6	TSL:1	c.397+548C>T		intron	N/A	ENSP00000378637.2	P28289-1
	TMOD1	ENST00000950655.1		c.520+548C>T		intron	N/A	ENSP00000620714.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81273 AN: 151686 Hom.: 22026 Cov.: 30

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.536 AC: 81334 AN: 151802 Hom.: 22043 Cov.: 30 AF XY: 0.531 AC XY: 39411 AN XY: 74184

African (AFR) AF: 0.592 AC: 24473 AN: 41362

American (AMR) AF: 0.450 AC: 6871 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1704 AN: 3462

East Asian (EAS) AF: 0.378 AC: 1941 AN: 5132

South Asian (SAS) AF: 0.518 AC: 2485 AN: 4796

European-Finnish (FIN) AF: 0.536 AC: 5650 AN: 10544

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36424 AN: 67928

Other (OTH) AF: 0.504 AC: 1064 AN: 2112

Alfa AF: 0.533 Hom.: 67633

Bravo AF: 0.530

Asia WGS AF: 0.434 AC: 1509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-0.47
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: rs1475545; hg19: chr9-100316230; COSMIC: COSV52246055; COSMIC: COSV52246055;