chr9-97551511-C-T

Position:

• chr9-97551511-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.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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMOD1	NM_003275.4	c.278-1770C>T		intron_variant		ENST00000259365.9	NP_003266.1
TMOD1	NM_001166116.2	c.278-1770C>T		intron_variant			NP_001159588.1
TMOD1	XM_047423825.1	c.-131-1770C>T		intron_variant			XP_047279781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMOD1	ENST00000259365.9	c.278-1770C>T		intron_variant		1	NM_003275.4	ENSP00000259365.3
TMOD1	ENST00000395211.6	c.278-1770C>T		intron_variant		1		ENSP00000378637.2

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

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.766

Alfa AF: 0.796 Hom.: 75740

Bravo AF: 0.767

Asia WGS AF: 0.796 AC: 2769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.95
DANN	Benign	0.64

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: rs4743106; hg19: chr9-100313793;