16-669612-C-T

Variant names:

• chr16-669612-C-T
• rs146979636
• NM_138769.3:c.276+6C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_138769.3(RHOT2):​c.276+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,611,200 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (14 hom.)
• Consequence: RHOT2 NM_138769.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002828
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.614
• Publications: 1 publications found

Genes affected

RHOT2 (HGNC:21169): (ras homolog family member T2) This gene encodes a member of the Rho family of GTPases. The encoded protein is localized to the outer mitochondrial membrane and plays a role in mitochondrial trafficking and fusion-fission dynamics. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-669612-C-T is Benign according to our data. Variant chr16-669612-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 777019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 14 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138769.3. 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
	RHOT2	NM_138769.3	MANE Select	c.276+6C>T		splice_region intron	N/A	NP_620124.1	Q8IXI1-1
	RHOT2	NM_001352275.2		c.276+6C>T		splice_region intron	N/A	NP_001339204.1	A0A8V8TM48
	RHOT2	NM_001352276.2		c.223-511C>T		intron	N/A	NP_001339205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOT2	ENST00000315082.9	TSL:1 MANE Select	c.276+6C>T		splice_region intron	N/A	ENSP00000321971.4	Q8IXI1-1
	RHOT2	ENST00000697194.1		c.276+6C>T		splice_region intron	N/A	ENSP00000513180.1	A0A8V8TM48
	RHOT2	ENST00000958324.1		c.276+6C>T		splice_region intron	N/A	ENSP00000628383.1

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152194 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00341

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00222 AC: 550 AN: 248294 AF XY: 0.00210

Gnomad AFR exome AF: 0.000498

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00234

Gnomad NFE exome AF: 0.00421

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00329 AC: 4799 AN: 1458888 Hom.: 14 Cov.: 31 AF XY: 0.00313 AC XY: 2273 AN XY: 725720

African (AFR) AF: 0.000508 AC: 17 AN: 33474

American (AMR) AF: 0.000313 AC: 14 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86190

European-Finnish (FIN) AF: 0.00332 AC: 169 AN: 50980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00402 AC: 4471 AN: 1111594

Other (OTH) AF: 0.00204 AC: 123 AN: 60356

GnomAD4 genome AF: 0.00184 AC: 280 AN: 152312 Hom.: 1 Cov.: 33 AF XY: 0.00156 AC XY: 116 AN XY: 74474

African (AFR) AF: 0.000553 AC: 23 AN: 41568

American (AMR) AF: 0.000392 AC: 6 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00341 AC: 232 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00255 Hom.: 0

Bravo AF: 0.00179

EpiCase AF: 0.00289

EpiControl AF: 0.00285

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		-0.61
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.0040
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: rs146979636; hg19: chr16-719612;