NM_030965.3:c.224G>A

Variant names:

• chr1-76868705-G-A
• rs952554580
• NM_030965.3:c.224G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030965.3(ST6GALNAC5):​c.224G>A​(p.Arg75Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,532,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R75L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ST6GALNAC5 NM_030965.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.372
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114714086).

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.224G>A	p.Arg75Gln	missense	Exon 2 of 5	NP_112227.1	Q9BVH7
	ST6GALNAC5	NM_001320273.2		c.224G>A	p.Arg75Gln	missense	Exon 2 of 4	NP_001307202.1	B4DV27
	ST6GALNAC5	NM_001320274.2		c.224G>A	p.Arg75Gln	missense	Exon 2 of 3	NP_001307203.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST6GALNAC5	ENST00000477717.6	TSL:1 MANE Select	c.224G>A	p.Arg75Gln	missense	Exon 2 of 5	ENSP00000417583.1	Q9BVH7
	ST6GALNAC5	ENST00000857213.1		c.224G>A	p.Arg75Gln	missense	Exon 2 of 4	ENSP00000527272.1
	ST6GALNAC5	ENST00000857212.1		c.224G>A	p.Arg75Gln	missense	Exon 2 of 4	ENSP00000527271.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152026 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000398 AC: 5 AN: 125542 AF XY: 0.0000582

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000199

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000214

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000138 AC: 19 AN: 1380760 Hom.: 0 Cov.: 31 AF XY: 0.0000162 AC XY: 11 AN XY: 680884

African (AFR) AF: 0.00 AC: 0 AN: 30522

American (AMR) AF: 0.000158 AC: 5 AN: 31610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23742

East Asian (EAS) AF: 0.00 AC: 0 AN: 35254

South Asian (SAS) AF: 0.0000260 AC: 2 AN: 76892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5584

European-Non Finnish (NFE) AF: 0.0000103 AC: 11 AN: 1072974

Other (OTH) AF: 0.0000175 AC: 1 AN: 57082

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152026 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74242

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.000196 AC: 3 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.37
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.11
Sift	Benign	0.41	T
Sift4G	Benign	0.58	T
Polyphen		0.92	P
Vest4		0.15
MutPred		0.44		Loss of methylation at R75 (P = 0.0528)
MVP		0.20
MPC		0.39
ClinPred		0.26	T
GERP RS		4.2
Varity_R		0.10
gMVP		0.22
Mutation Taster		=89/11	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: rs952554580; hg19: chr1-77334390;