NM_016548.4:c.978C>T

Variant names:

• chr9-86035405-G-A
• rs139831634
• NM_016548.4:c.978C>T

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_016548.4(GOLM1):​c.978C>T​(p.Pro326Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,613,898 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (5 hom., cov: 30)
  • Exomes 𝑓: 0.0016 (19 hom.)
• Consequence: GOLM1 NM_016548.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.94
• Publications: 1 publications found

Genes affected

GOLM1 (HGNC:15451): (golgi membrane protein 1) The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a type II Golgi transmembrane protein. It processes proteins synthesized in the rough endoplasmic reticulum and assists in the transport of protein cargo through the Golgi apparatus. The expression of this gene has been observed to be upregulated in response to viral infection. Alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-86035405-G-A is Benign according to our data. Variant chr9-86035405-G-A is described in ClinVar as Benign. ClinVar VariationId is 713718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.94 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00656 (997/152080) while in subpopulation AFR AF = 0.0191 (792/41494). AF 95% confidence interval is 0.018. There are 5 homozygotes in GnomAd4. There are 478 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016548.4. 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
	GOLM1	NM_016548.4	MANE Select	c.978C>T	p.Pro326Pro	synonymous	Exon 8 of 10	NP_057632.2
	GOLM1	NM_177937.3		c.978C>T	p.Pro326Pro	synonymous	Exon 8 of 10	NP_808800.1	Q8NBJ4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLM1	ENST00000388712.7	TSL:1 MANE Select	c.978C>T	p.Pro326Pro	synonymous	Exon 8 of 10	ENSP00000373364.3	Q8NBJ4-1
	GOLM1	ENST00000388711.7	TSL:1	c.978C>T	p.Pro326Pro	synonymous	Exon 8 of 10	ENSP00000373363.3	Q8NBJ4-1
	GOLM1	ENST00000944326.1		c.1020C>T	p.Pro340Pro	synonymous	Exon 8 of 10	ENSP00000614385.1

Frequencies

GnomAD3 genomes AF: 0.00653 AC: 992 AN: 151962 Hom.: 5 Cov.: 30

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00361

Gnomad ASJ AF: 0.0174

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00287 AC: 722 AN: 251328 AF XY: 0.00243

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.0152

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00107

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00157 AC: 2294 AN: 1461818 Hom.: 19 Cov.: 35 AF XY: 0.00151 AC XY: 1096 AN XY: 727198

African (AFR) AF: 0.0234 AC: 784 AN: 33478

American (AMR) AF: 0.00239 AC: 107 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 391 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86254

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53380

Middle Eastern (MID) AF: 0.00505 AC: 29 AN: 5746

European-Non Finnish (NFE) AF: 0.000620 AC: 690 AN: 1112008

Other (OTH) AF: 0.00437 AC: 264 AN: 60392

GnomAD4 genome AF: 0.00656 AC: 997 AN: 152080 Hom.: 5 Cov.: 30 AF XY: 0.00643 AC XY: 478 AN XY: 74316

African (AFR) AF: 0.0191 AC: 792 AN: 41494

American (AMR) AF: 0.00360 AC: 55 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0174 AC: 60 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4808

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10584

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00100 AC: 68 AN: 67988

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

Alfa AF: 0.00464 Hom.: 8

Bravo AF: 0.00761

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00136

EpiControl AF: 0.00172

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	-0.81
CADD	Benign	0.13
DANN	Benign	0.49
PhyloP100		-4.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139831634; hg19: chr9-88650320;