rs16964508

Positions:

• chr15-51765987-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014548.4(TMOD2):​c.-69-386A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0317 in 152,262 control chromosomes in the GnomAD database, including 122 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 0.032 (122 hom., cov: 33)
• Consequence: TMOD2 NM_014548.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

TMOD2 (HGNC:11872): (tropomodulin 2) This gene encodes a neuronal-specific member of the tropomodulin family of actin-regulatory proteins. The encoded protein caps the pointed end of actin filaments preventing both elongation and depolymerization. The capping activity of this protein is dependent on its association with tropomyosin. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0317 (4825/152262) while in subpopulation NFE AF= 0.0501 (3405/68002). AF 95% confidence interval is 0.0487. There are 122 homozygotes in gnomad4. There are 2338 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 122 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMOD2	NM_014548.4	c.-69-386A>G		intron_variant		ENST00000249700.9	NP_055363.1
TMOD2	NM_001142885.2	c.-69-386A>G		intron_variant			NP_001136357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMOD2	ENST00000249700.9	c.-69-386A>G		intron_variant		1	NM_014548.4	ENSP00000249700	P1
TMOD2	ENST00000435126.6	c.-69-386A>G		intron_variant		2		ENSP00000404590
TMOD2	ENST00000539962.6	c.-283-386A>G		intron_variant		2		ENSP00000437743
TMOD2	ENST00000560576.1	n.99-386A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4823 AN: 152144 Hom.: 121 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.0121

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0167

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

GnomAD4 genome AF: 0.0317 AC: 4825 AN: 152262 Hom.: 122 Cov.: 33 AF XY: 0.0314 AC XY: 2338 AN XY: 74452

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0130

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.0122

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.0538

Gnomad4 NFE AF: 0.0501

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0439 Hom.: 72

Bravo AF: 0.0273

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.087
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs16964508; hg19: chr15-52058184;