NM_152574.3:c.1620A>G

Variant names:

• chr9-15177720-T-C
• rs77494837
• NM_152574.3:c.1620A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_152574.3(TTC39B):​c.1620A>G​(p.Leu540Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,613,138 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (58 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (38 hom.)
• Consequence: TTC39B NM_152574.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.170
• Publications: 0 publications found

Genes affected

TTC39B (HGNC:23704): (tetratricopeptide repeat domain 39B) Predicted to be involved in several processes, including cholesterol homeostasis; negative regulation of cholesterol storage; and regulation of cholesterol efflux. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 9-15177720-T-C is Benign according to our data. Variant chr9-15177720-T-C is described in ClinVar as Benign. ClinVar VariationId is 768279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.17 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0145 (2214/152234) while in subpopulation AFR AF = 0.0505 (2096/41532). AF 95% confidence interval is 0.0487. There are 58 homozygotes in GnomAd4. There are 1038 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152574.3. 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
	TTC39B	NM_152574.3	MANE Select	c.1620A>G	p.Leu540Leu	synonymous	Exon 18 of 20	NP_689787.3	A0A8V8PNE1
	TTC39B	NM_001168339.2		c.1614A>G	p.Leu538Leu	synonymous	Exon 18 of 20	NP_001161811.2
	TTC39B	NM_001168340.2		c.1581A>G	p.Leu527Leu	synonymous	Exon 17 of 19	NP_001161812.2	A0A8V8NCV2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC39B	ENST00000512701.7	TSL:2 MANE Select	c.1620A>G	p.Leu540Leu	synonymous	Exon 18 of 20	ENSP00000422496.2	A0A8V8PNE1
	TTC39B	ENST00000380853.1	TSL:1	n.640A>G		non_coding_transcript_exon	Exon 5 of 7
	TTC39B	ENST00000380850.9	TSL:2	c.1581A>G	p.Leu527Leu	synonymous	Exon 17 of 19	ENSP00000370231.5	A0A8V8NCV2

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2206 AN: 152116 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00390 AC: 977 AN: 250762 AF XY: 0.00270

Gnomad AFR exome AF: 0.0521

Gnomad AMR exome AF: 0.00238

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00148 AC: 2168 AN: 1460904 Hom.: 38 Cov.: 30 AF XY: 0.00122 AC XY: 888 AN XY: 726776

African (AFR) AF: 0.0508 AC: 1698 AN: 33408

American (AMR) AF: 0.00260 AC: 116 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39652

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5766

European-Non Finnish (NFE) AF: 0.0000954 AC: 106 AN: 1111520

Other (OTH) AF: 0.00358 AC: 216 AN: 60344

GnomAD4 genome AF: 0.0145 AC: 2214 AN: 152234 Hom.: 58 Cov.: 32 AF XY: 0.0139 AC XY: 1038 AN XY: 74446

African (AFR) AF: 0.0505 AC: 2096 AN: 41532

American (AMR) AF: 0.00549 AC: 84 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68012

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00679 Hom.: 24

Bravo AF: 0.0173

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000297

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.6
DANN	Benign	0.60
PhyloP100		-0.17
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: rs77494837; hg19: chr9-15177718;