7-48005993-C-T

Variant names:

• chr7-48005993-C-T
• rs773133097
• NM_001030019.2:c.553G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001030019.2(SUN3):​c.553G>A​(p.Ala185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,792 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A185P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUN3 NM_001030019.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.40
• Publications: 0 publications found

Genes affected

SUN3 (HGNC:22429): (Sad1 and UNC84 domain containing 3) Predicted to enable protein-membrane adaptor activity. Predicted to be involved in nuclear envelope organization. Predicted to be integral component of nuclear inner membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28873426).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030019.2. 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
	SUN3	NM_001030019.2	MANE Select	c.553G>A	p.Ala185Thr	missense	Exon 6 of 10	NP_001025190.1	Q8TAQ9-1
	SUN3	NM_152782.4		c.553G>A	p.Ala185Thr	missense	Exon 7 of 11	NP_689995.3
	SUN3	NM_001284350.2		c.517G>A	p.Ala173Thr	missense	Exon 7 of 11	NP_001271279.1	Q8TAQ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN3	ENST00000297325.9	TSL:5 MANE Select	c.553G>A	p.Ala185Thr	missense	Exon 6 of 10	ENSP00000297325.4	Q8TAQ9-1
	SUN3	ENST00000395572.6	TSL:1	c.553G>A	p.Ala185Thr	missense	Exon 7 of 11	ENSP00000378939.2	Q8TAQ9-1
	SUN3	ENST00000438771.5	TSL:1	c.253G>A	p.Ala85Thr	missense	Exon 3 of 8	ENSP00000409077.1	Q8TAQ9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460792 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726734

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	0.0062	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.080
Sift	Benign	0.057	T
Sift4G	Benign	0.29	T
Polyphen		1.0	D
Vest4		0.57
MutPred		0.44		Gain of glycosylation at A185 (P = 0.0494)
MVP		0.29
MPC		0.20
ClinPred		0.94	D
GERP RS		5.5
PromoterAI		-0.027	Neutral
Varity_R		0.098
gMVP		0.34
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs773133097; hg19: chr7-48045590;