rs764138

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC100887080		n.20732150A>G		intragenic_variant
ACSM3	XM_047434419.1	c.-294+411A>G		intron_variant	Intron 3 of 18		XP_047290375.1
ACSM3	XM_047434420.1	c.-294+411A>G		intron_variant	Intron 5 of 20		XP_047290376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACSM3	ENST00000568235.5	c.-189-17760A>G		intron_variant	Intron 1 of 4	4		ENSP00000457003.1
ACSM3	ENST00000561584.5	c.-189-17760A>G		intron_variant	Intron 1 of 3	4		ENSP00000456055.1
ACSM3	ENST00000501740.6	n.606-17115A>G		intron_variant	Intron 2 of 4	5

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 v4.3

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;