chr1-77044267-C-G

Variant names:

• chr1-77044267-C-G
• rs746598078
• NM_030965.3:c.325C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030965.3(ST6GALNAC5):​c.325C>G​(p.Arg109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R109Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: ST6GALNAC5 NM_030965.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 4 publications found

Genes affected

ST6GALNAC5 (HGNC:19342): (ST6 N-acetylgalactosaminide alpha-2,6-sialyltransferase 5) The protein encoded by this gene is a Golgi type II transmembrane glycosyltransferase. The encoded protein catalyzes the transfer of sialic acid to cell surface proteins to modulate cell-cell interactions. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034620136).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030965.3. 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
	ST6GALNAC5	NM_030965.3	MANE Select	c.325C>G	p.Arg109Gly	missense	Exon 3 of 5	NP_112227.1	Q9BVH7
	ST6GALNAC5	NM_001320273.2		c.262-5991C>G		intron	N/A	NP_001307202.1	B4DV27
	ST6GALNAC5	NM_001320274.2		c.262-18708C>G		intron	N/A	NP_001307203.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC5	ENST00000477717.6	TSL:1 MANE Select	c.325C>G	p.Arg109Gly	missense	Exon 3 of 5	ENSP00000417583.1	Q9BVH7
	ST6GALNAC5	ENST00000857213.1		c.325C>G	p.Arg109Gly	missense	Exon 3 of 4	ENSP00000527272.1
	ST6GALNAC5	ENST00000857212.1		c.262-5995C>G		intron	N/A	ENSP00000527271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250950 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461670 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.46
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.16	N
PhyloP100		0.20
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.077
Sift	Benign	0.63	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.53		Loss of solvent accessibility (P = 0.0159)
MVP		0.043
MPC		0.44
ClinPred		0.0093	T
GERP RS		1.4
Varity_R		0.13
gMVP		0.26
Mutation Taster		=81/19	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: rs746598078; hg19: chr1-77509952; COSMIC: COSV59564346;