rs375513503

Variant names:

• chr10-97865607-C-G
• rs375513503
• NM_001010917.3:c.411C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-97865607-C-G
• chr10-97865607-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001010917.3(GOLGA7B):​c.411C>G​(p.Tyr137*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Y137Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GOLGA7B NM_001010917.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 0 publications found

Genes affected

GOLGA7B (HGNC:31668): (golgin A7 family member B) Enables enzyme binding activity. Predicted to be involved in peptidyl-L-cysteine S-palmitoylation and protein targeting to membrane. Predicted to be located in Golgi membrane. Predicted to be part of palmitoyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

CRTAC1 (HGNC:14882): (cartilage acidic protein 1) This gene encodes a glycosylated extracellular matrix protein that is found in the interterritorial matrix of articular deep zone cartilage. This protein is used as a marker to distinguish chondrocytes from osteoblasts and mesenchymal stem cells in culture. The presence of FG-GAP motifs and an RGD integrin-binding motif suggests that this protein may be involved in cell-cell or cell-matrix interactions. Copy number alterations in this gene have been observed in neurofibromatosis type 1-associated glomus tumors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010917.3. 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
	GOLGA7B	NM_001010917.3	MANE Select	c.411C>G	p.Tyr137*	stop_gained	Exon 5 of 5	NP_001010917.1	Q2TAP0
	CRTAC1	NM_018058.7	MANE Select	c.1927G>C	p.Val643Leu	missense	Exon 15 of 15	NP_060528.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA7B	ENST00000370602.6	TSL:1 MANE Select	c.411C>G	p.Tyr137*	stop_gained	Exon 5 of 5	ENSP00000359634.1	Q2TAP0
	CRTAC1	ENST00000370597.8	TSL:1 MANE Select	c.1927G>C	p.Val643Leu	missense	Exon 15 of 15	ENSP00000359629.3	Q9NQ79-1
	GOLGA7B	ENST00000856898.1		c.411C>G	p.Tyr137*	stop_gained	Exon 6 of 6	ENSP00000526957.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248562 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000900

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461268 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726860

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111596

Other (OTH) AF: 0.00 AC: 0 AN: 60366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000193 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.13
Sift	Benign	0.045	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0020	B
Vest4		0.15
MutPred		0.17		Loss of sheet (P = 0.0228)
MVP		0.53
MPC		0.33
ClinPred		0.69	D
GERP RS		-0.0010
Varity_R		0.052
gMVP		0.31
Mutation Taster		=32/168	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs375513503; hg19: chr10-99625364;