rs16964508

Variant names:

• chr15-51765987-A-G
• rs16964508
• NM_014548.4:c.-69-386A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 122 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014548.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMOD2	NM_014548.4	MANE Select	c.-69-386A>G		intron	N/A	NP_055363.1
	TMOD2	NM_001142885.2		c.-69-386A>G		intron	N/A	NP_001136357.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMOD2	ENST00000249700.9	TSL:1 MANE Select	c.-69-386A>G		intron	N/A	ENSP00000249700.4
	TMOD2	ENST00000435126.6	TSL:2	c.-69-386A>G		intron	N/A	ENSP00000404590.2
	TMOD2	ENST00000539962.6	TSL:2	c.-283-386A>G		intron	N/A	ENSP00000437743.2

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

African (AFR) AF: 0.0105 AC: 435 AN: 41572

American (AMR) AF: 0.0130 AC: 199 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5184

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4820

European-Finnish (FIN) AF: 0.0538 AC: 571 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0501 AC: 3405 AN: 68002

Other (OTH) AF: 0.0166 AC: 35 AN: 2112

Alfa AF: 0.0439 Hom.: 79

Bravo AF: 0.0273

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.087
DANN	Benign	0.40
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs16964508; hg19: chr15-52058184;