16-20732150-A-G

Variant names:

• chr16-20732150-A-G
• rs764138

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.487 in 151,942 control chromosomes in the GnomAD database, including 18,939 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 0.49 (18939 hom., cov: 31)
• Consequence: LOC100887080 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194
• Publications: 9 publications found

Genes affected

LOC100887080 (HGNC:):

ACSM3 (HGNC:10522): (acyl-CoA synthetase medium chain family member 3) Enables butyrate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. Implicated in IgA glomerulonephritis. Biomarker of ulcerative colitis. [provided by Alliance of Genome Resources, Apr 2022]

THUMPD1 (HGNC:23807): (THUMP domain containing 1) Enables RNA binding activity. Predicted to be involved in tRNA modification. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

THUMPD1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with speech delay and variable ocular anomalies

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000568235.5. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACSM3	ENST00000568235.5	TSL:4	c.-189-17760A>G		intron	N/A	ENSP00000457003.1
	ACSM3	ENST00000561584.5	TSL:4	c.-189-17760A>G		intron	N/A	ENSP00000456055.1
	ACSM3	ENST00000501740.6	TSL:5	n.606-17115A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73938 AN: 151824 Hom.: 18933 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.487 AC: 73956 AN: 151942 Hom.: 18939 Cov.: 31 AF XY: 0.483 AC XY: 35848 AN XY: 74270

African (AFR) AF: 0.375 AC: 15530 AN: 41458

American (AMR) AF: 0.463 AC: 7066 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1434 AN: 3466

East Asian (EAS) AF: 0.143 AC: 738 AN: 5154

South Asian (SAS) AF: 0.422 AC: 2035 AN: 4820

European-Finnish (FIN) AF: 0.574 AC: 6057 AN: 10552

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.584 AC: 39634 AN: 67914

Other (OTH) AF: 0.477 AC: 1004 AN: 2106

Alfa AF: 0.551 Hom.: 11921

Bravo AF: 0.470

Asia WGS AF: 0.302 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs764138; hg19: chr16-20743472;