9-97553948-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMOD1	NM_003275.4	c.397+548C>T		intron_variant		ENST00000259365.9
TMOD1	NM_001166116.2	c.397+548C>T		intron_variant
TMOD1	XM_047423825.1	c.-12+548C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMOD1	ENST00000259365.9	c.397+548C>T		intron_variant		1	NM_003275.4	P1
TMOD1	ENST00000395211.6	c.397+548C>T		intron_variant		1		P1

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

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.504

Alfa AF: 0.531 Hom.: 27577

Bravo AF: 0.530

Asia WGS AF: 0.434 AC: 1509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.8
Dann	Benign	0.75

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: rs1475545; hg19: chr9-100316230; COSMIC: COSV52246055; COSMIC: COSV52246055;