7-832547-T-G

Variant names:

• chr7-832547-T-G
• NM_001130965.3:c.23T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001130965.3(SUN1):​c.23T>G​(p.Met8Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,220 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

Genes affected

SUN1 (HGNC:18587): (Sad1 and UNC84 domain containing 1) This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2019]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3	c.23T>G	p.Met8Arg	missense_variant	Exon 1 of 19	ENST00000401592.6	NP_001124437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6	c.23T>G	p.Met8Arg	missense_variant	Exon 1 of 19	1	NM_001130965.3	ENSP00000384015.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461220 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726798

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.0064	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	.;.;.;T;T;T;.;T;T;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.95	D;D;D;.;D;D;D;D;D;D;D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;.;.;.;.;.;.;.;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.5	D;N;D;D;D;D;D;D;N;N;D
REVEL	Benign	0.20
Sift	Uncertain	0.010	D;D;D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.015	D;T;D;D;D;D;D;D;D;D;D
Vest4		0.74
MutPred		0.14		.;Gain of disorder (P = 0.07);Gain of disorder (P = 0.07);Gain of disorder (P = 0.07);Gain of disorder (P = 0.07);Gain of disorder (P = 0.07);Gain of disorder (P = 0.07);Gain of disorder (P = 0.07);Gain of disorder (P = 0.07);Gain of disorder (P = 0.07);Gain of disorder (P = 0.07);
MVP		0.35
MPC		0.22
ClinPred		0.55	D
GERP RS		-0.28
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.76		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.76		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-872184;