rs139713563

Variant names:

• chr16-20737067-G-C
• rs139713563
• NM_017736.5:c.875C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-20737067-G-C
• chr16-20737067-G-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_017736.5(THUMPD1):​c.875C>G​(p.Ala292Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THUMPD1 NM_017736.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0970
• Publications: 0 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03563112).
• BP6: Variant 16-20737067-G-C is Benign according to our data. Variant chr16-20737067-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3177257.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017736.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THUMPD1	NM_017736.5	MANE Select	c.875C>G	p.Ala292Gly	missense	Exon 4 of 4	NP_060206.2
	THUMPD1	NM_001304550.2		c.875C>G	p.Ala292Gly	missense	Exon 4 of 5	NP_001291479.1	Q9NXG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THUMPD1	ENST00000396083.7	TSL:1 MANE Select	c.875C>G	p.Ala292Gly	missense	Exon 4 of 4	ENSP00000379392.2	Q9NXG2
	THUMPD1	ENST00000381337.6	TSL:1	c.875C>G	p.Ala292Gly	missense	Exon 4 of 5	ENSP00000370741.2	Q9NXG2
	THUMPD1	ENST00000888379.1		c.875C>G	p.Ala292Gly	missense	Exon 4 of 5	ENSP00000558438.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.94
DANN	Benign	0.55
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N
PhyloP100		-0.097
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.048
Sift	Benign	0.43	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.038
MutPred		0.16		Loss of stability (P = 0.0145)
MVP		0.25
MPC		0.18
ClinPred		0.018	T
GERP RS		-5.4
Varity_R		0.031
gMVP		0.13

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: rs139713563; hg19: chr16-20748389;