chr10-16764493-C-T

Variant names:

• chr10-16764493-C-T
• rs141892985
• NM_012425.4:c.178G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_012425.4(RSU1):​c.178G>A​(p.Ala60Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00109 in 1,613,440 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00069 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: RSU1 NM_012425.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.65
• Publications: 3 publications found

Genes affected

RSU1 (HGNC:10464): (Ras suppressor protein 1) This gene encodes a protein that is involved in the Ras signal transduction pathway, growth inhibition, and nerve-growth factor induced differentiation processes, as determined in mouse and human cell line studies. In mouse, the encoded protein was initially isolated based on its ability to inhibit v-Ras transformation. Multiple alternatively spliced transcript variants for this gene have been reported; one of these variants was found only in glioma tumors. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04973805).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSU1	NM_012425.4	c.178G>A	p.Ala60Thr	missense_variant	Exon 4 of 9	ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.19G>A	p.Ala7Thr	missense_variant	Exon 3 of 8		NP_689937.2
RSU1	XM_047425617.1	c.178G>A	p.Ala60Thr	missense_variant	Exon 3 of 7		XP_047281573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSU1	ENST00000345264.10	c.178G>A	p.Ala60Thr	missense_variant	Exon 4 of 9	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes AF: 0.000690 AC: 105 AN: 152078 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000753 AC: 189 AN: 250878 AF XY: 0.000752

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00142

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.00113 AC: 1651 AN: 1461244 Hom.: 0 Cov.: 31 AF XY: 0.00111 AC XY: 809 AN XY: 726922

African (AFR) AF: 0.000239 AC: 8 AN: 33454

American (AMR) AF: 0.000134 AC: 6 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86142

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00140 AC: 1551 AN: 1111660

Other (OTH) AF: 0.000779 AC: 47 AN: 60360

GnomAD4 genome AF: 0.000690 AC: 105 AN: 152196 Hom.: 2 Cov.: 32 AF XY: 0.000645 AC XY: 48 AN XY: 74414

African (AFR) AF: 0.000241 AC: 10 AN: 41498

American (AMR) AF: 0.00 AC: 0 AN: 15284

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10592

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

European-Non Finnish (NFE) AF: 0.00134 AC: 91 AN: 68016

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00113 Hom.: 1

Bravo AF: 0.000688

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.000815 AC: 99

EpiCase AF: 0.000709

EpiControl AF: 0.000771

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.178G>A (p.A60T) alteration is located in exon 4 (coding exon 3) of the RSU1 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the alanine (A) at amino acid position 60 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T;T;.
Eigen	Benign	-0.035
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.96	.;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.050	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L;.
PhyloP100		5.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.0	N;N;.
REVEL	Benign	0.067
Sift	Benign	0.13	T;T;.
Sift4G	Benign	0.14	T;T;.
Polyphen		0.095	B;B;.
Vest4		0.48
MVP		0.56
MPC		0.29
ClinPred		0.039	T
GERP RS		4.7
Varity_R		0.24
gMVP		0.39
Mutation Taster		=95/5	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: rs141892985; hg19: chr10-16806492; COSMIC: COSV99061199; COSMIC: COSV99061199;