1-32075035-A-T

Variant names:

• chr1-32075035-A-T
• rs1051594832
• NM_018056.4:c.89A>T

Variant summary

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

The NM_018056.4(TMEM39B):​c.89A>T​(p.His30Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000357 in 1,399,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: TMEM39B NM_018056.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.62
• Publications: 1 publications found

Genes affected

TMEM39B (HGNC:25510): (transmembrane protein 39B) Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.19375217).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018056.4. 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
	TMEM39B	NM_018056.4	MANE Select	c.89A>T	p.His30Leu	missense	Exon 2 of 9	NP_060526.2	Q9GZU3-1
	TMEM39B	NM_001319677.2		c.-293A>T		5_prime_UTR	Exon 2 of 9	NP_001306606.1	Q9NW51
	TMEM39B	NM_001319678.2		c.-273A>T		5_prime_UTR	Exon 2 of 7	NP_001306607.1	Q9GZU3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM39B	ENST00000336294.10	TSL:1 MANE Select	c.89A>T	p.His30Leu	missense	Exon 2 of 9	ENSP00000338165.5	Q9GZU3-1
	TMEM39B	ENST00000441402.5	TSL:1	n.89A>T		non_coding_transcript_exon	Exon 2 of 7	ENSP00000390889.1	F8WB89
	TMEM39B	ENST00000969125.1		c.89A>T	p.His30Leu	missense	Exon 2 of 10	ENSP00000639184.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000640 AC: 1 AN: 156202 AF XY: 0.0000121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1399284 Hom.: 0 Cov.: 30 AF XY: 0.00000435 AC XY: 3 AN XY: 690166

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25166

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.00 AC: 0 AN: 79218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000463 AC: 5 AN: 1078924

Other (OTH) AF: 0.00 AC: 0 AN: 58000

GnomAD4 genome Cov.: 32

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	0.093
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.052	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.14
Sift	Benign	0.46	T
Sift4G	Benign	1.0	T
Polyphen		0.99	D
Vest4		0.44
MutPred		0.22		Gain of sheet (P = 0.0344)
MVP		0.34
MPC		1.2
ClinPred		0.52	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.084
gMVP		0.45
Mutation Taster		=56/44	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: rs1051594832; hg19: chr1-32540636;